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Physicists create five-lane superhighway for electrons

Work could lead to ultra-efficient electronics and more.

Elizabeth A. Thomson | Materials Research Laboratory

blue and purple highway

Artist’s rendition of the superhighway for electrons that can occur in rhombohedral graphene, a special kind of graphite (pencil lead).

Credit: Sampson Wilcox, MIT Research Laboratory of Electronics

MIT physicists and colleagues have created a five-lane superhighway for electrons that could allow ultra-efficient electronics and more. The work, reported in the May 9 issue of Science , is one of several important discoveries by the same team over the last year involving a material that is essentially a unique form of pencil lead.

“This discovery has direct implications for low-power electronic devices because no energy is lost during the propagation of electrons, which is not the case in regular materials where the electrons are scattered,” says Long Ju, an assistant professor in the MIT Department of Physics and corresponding author of the Science paper.

The phenomenon is akin to cars traveling down an open turnpike as opposed to those moving through neighborhoods. The neighborhood cars can be stopped or slowed by other drivers making abrupt stops or U-turns that disrupt an otherwise smooth commute.

A New Material

The material behind this work, known as rhombohedral pentalayer graphene, was discovered two years ago by physicists led by Ju. “We found a goldmine, and every scoop is revealing something new,” says Ju, who is also affiliated with MIT’s Materials Research Laboratory.

In a Nature Nanotechnology paper last October Ju and colleagues reported the discovery of three important properties arising from rhombohedral graphene. For example, they showed that it could be topological, or allow the unimpeded movement of electrons around the edge of the material but not through the middle. That resulted in a superhighway, but required the application of a large magnetic field some tens of thousands times stronger than the Earth’s magnetic field.

In the current work, the team reports creating the superhighway without any magnetic field.

people in lab

Tonghang Han, an MIT graduate student in physics, is a co-first author of the paper. “We are not the first to discover this general phenomenon, but we did so in a very different system. And compared to previous systems, ours is simpler and also supports more electron channels.” Explains Ju, “other materials can only support one lane of traffic on the edge of the material. We suddenly bumped it up to five.”

Additional co-first authors of the paper who contributed equally to the work are Zhengguang Lu and Yuxuan Yao. Lu is a postdoctoral associate in the Materials Research Laboratory. Yao conducted the work as a visiting undergraduate student from Tsinghua University. Other authors are MIT Professor Liang Fu of physics;   Jixiang Yang and Junseok Seo, both graduate students in MIT physics; Chiho Yoon and Fan Zhang of the University of Texas at Dallas; and Kenji Watanabe and Takashi Taniguchi of the National Institute for Materials Science in Japan.

How it Works

Pencil lead, or graphite, is composed of graphene, a single layer of carbon atoms arranged in hexagons resembling a honeycomb structure. Rhombohedral graphene is composed of five layers of graphene stacked in a specific overlapping order.

Ju and colleagues isolated rhombohedral graphene thanks to a novel microscope Ju built at MIT in 2021 that can quickly and relatively inexpensively determine a variety of important characteristics of a material at the nanoscale. Pentalayer rhombohedral stacked graphene is only a few billionths of a meter thick.

In the current work, the team tinkered with the original system, adding a layer of tungsten disulfide (WS 2 ). “The interaction between the WS 2 and the pentalayer rhombohedral graphene resulted in this five-lane superhighway that operates at zero magnetic field,” says Ju.

Comparison to Superconductivity

The phenomenon that the Ju group discovered in rhombohedral graphene that allows electrons to travel with no resistance at zero magnetic field is known as the quantum anomalous Hall effect. Most people are more familiar with superconductivity, a completely different phenomenon that does the same thing but happens in very different materials.

Ju notes that although superconductors were discovered in the 1910s, it took some 100 years of research to coax the system to work at the higher temperatures necessary for applications. “And the world record is still well below room temperature,” he notes.

Similarly, the rhombohedral graphene superhighway currently operates at about 2 Kelvin, or -456 Fahrenheit. “It will take a lot of effort to elevate the temperature, but as physicists , our job is to provide the insight; a different way for realizing this [phenomenon],” Ju says.

Very Exciting

The discoveries involving rhombohedral graphene came as a result of painstaking research that wasn’t guaranteed to work. “We tried many recipes over many months,” says Han, “so it was very exciting when we cooled the system to a very low temperature and [a five-lane superhighway operating at zero magnetic field] just popped out.”

Says Ju, “it’s very exciting to be the first to discover a phenomenon in a new system, especially in a material that we uncovered.”

This work was supported by a Sloan Fellowship; the U.S. National Science Foundation; the U.S. Office of the Under Secretary of Defense for Research and Engineering; the Japan Society for the Promotion of Science KAKENHI; and the World Premier International Research Initiative of Japan.

Making the Complicated Simple: A Minimizing Carrier Strategy on Innovative Nanopesticides

  • Open access
  • Published: 14 May 2024
  • Volume 16 , article number  193 , ( 2024 )

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research article in nanotechnology

  • Wenjie Shangguan 1 ,
  • Qiliang Huang 1 ,
  • Huiping Chen 1 ,
  • Yingying Zheng 1 , 3 ,
  • Pengyue Zhao 1 ,
  • Chong Cao 1 ,
  • Manli Yu 1 ,
  • Yongsong Cao 2 &
  • Lidong Cao 1  

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Nanopesticides with minimizing carrier were prepared through prodrug molecular design and molecular self-assembly.

Nanopesticides with minimizing carrier are expected to solve the environmental risks caused by the unrestricted introduction of nanomaterials.

Future development and challenges of nanopesticides with minimizing carrier.

The flourishing progress in nanotechnology offers boundless opportunities for agriculture, particularly in the realm of nanopesticides research and development. However, concerns have been raised regarding the human and environmental safety issues stemming from the unrestrained use of non-therapeutic nanomaterials in nanopesticides. It is also important to consider whether the current development strategy of nanopesticides based on nanocarriers can strike a balance between investment and return, and if the complex material composition genuinely improves the efficiency, safety, and circularity of nanopesticides. Herein, we introduced the concept of nanopesticides with minimizing carriers (NMC) prepared through prodrug design and molecular self-assembly emerging as practical tools to address the current limitations, and compared it with nanopesticides employing non-therapeutic nanomaterials as carriers (NNC). We further summarized the current development strategy of NMC and examined potential challenges in its preparation, performance, and production. Overall, we asserted that the development of NMC systems can serve as the innovative driving force catalyzing a green and efficient revolution in nanopesticides, offering a way out of the current predicament.

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1 Introduction

In the contemporary era, transformative changes are needed in agricultural and food systems to cope with the impacts of global climate change [ 1 ]. Pesticides are widely used as a vital component of this system, but the escalating issue of resistance conceals a substantial crisis [ 2 ]. Concerns regarding toxicity, pollution, and oversight have arisen successively [ 3 ]. Nowadays, science-driven advances form the cornerstone for addressing these challenges [ 4 ], with nanotechnology emerging as a promising frontier for revolutionizing pesticides [ 5 ]. Nanopesticides have emerged as a development with significant potential, and their importance and priority have been widely recognized [ 6 ]. In this field, using nanomaterials to load active ingredients stands out as a pivotal strategy for constructing nanoscale delivery platforms, which currently representing the most mainstream research and development concept. Compared with traditional pesticides, nanopesticides can be endowed with stimulus-responsive functions through specific materials and can be efficiently delivered to targets through small size effects [ 7 , 8 ]. Nanopesticides play a pivotal role in enhancing food security and fostering sustainable practices in crop protection [ 9 , 10 , 11 ].

As mentioned above, research strategy of nanopesticides is predominantly based on developing diverse nanomaterials as carriers to provide better release behavior, higher inhibition efficiency, and more functional features for this delivery system (Fig.  1 ). However, has the overall efficiency of current nanopesticides truly achieved a significant leap from millimeters or micrometers scales to nanometer scales? The size effect of nanopesticides is influenced by multiple factors, and arriving at more accurate conclusions necessitates prolonged and thorough discussions. Regrettably, existing research data does not appear to demonstrate that the enhancement of nanopesticides has achieved the most optimal results [ 12 ]. Simultaneously, it is crucial to emphasize that the development of pesticide products is highly dependent on cost considerations. In the present progression of nanopesticides, the excessive modification of nanomaterials within nanoscale delivery platforms through intricate processes often diverges from the core principles of sustainable development. This deviation is notable as sustainable development underscores efficiency, safety, and circularity, which are important guiding principles for nanopesticides research [ 13 , 14 ].

figure 1

Advantages and challenges of utilizing nanomaterials in nanopesticides

Given the background outlined above, the next crucial topic for in-depth discussion is the safety of current nanopesticide research strategies centered around nanomaterials. Compared with medicine, the process of pesticide delivery and application scenario are open and complex, involving the entire ecosystem, and its potential process losses and residual hazards receive widespread attention. Before nanopesticide products enter the market, the establishment of a comprehensive framework for risk assessment is imperative to ensure compliance with the demands of sustainable intensification in the future. On the one hand, the large-scale application of engineered nanomaterials (EEMs) has indeed promoted the development of nanopesticides, but, on the other hand, addressing the inherent risks and limitations of the unrestrained introduction and proliferation of nanomaterials will be a challenge [ 15 , 16 , 17 ]. Acknowledgment is necessary for the potential long-term adverse effects of EEMs on agroecosystems [ 18 ], encompassing spanning soil, plants, and various organisms, including humans [ 19 , 20 , 21 , 22 ] (Fig.  1 ). The introduction of EEMs may also cause indirectly the harmful of nanoplastics on biological systems, which posing a significant threat to agricultural sustainability and food safety [ 23 ]. Furthermore, existing analyses indicate that a stringent screening process for certain EEMs is necessary to ensure that they meet the conditions for maximizing the net realized benefits in a specific agricultural application [ 24 ]. Collectively, the balance between input costs (material, energy input, usage amount, and labor and time costs) and realized benefits (crop yield, germination rate, and disease incidence) of EEMs, the effectiveness of risk assessment system, and the prospects of large-scale application are still controversial. Indeed, these issues have started to impede the progress of nanopesticides.

How to advance the development and application of nanopesticides in the future while reducing dependence on nanomaterials is an urgent issue deserving serious consideration. It is noteworthy to emphasize the growing importance of carrier-free nanodrugs in the medical field [ 25 ], which providing a reference for getting out of the current predicament [ 26 , 27 ]. Carrier-free nanodrugs developed through prodrug preparation and molecular self-assembly exhibit exceptionally high loading capacity [ 28 ]. This system enhances overall safety through reducing non-therapeutic materials and increasing effective content. The advent of cost-effective and high-throughput self-assembly technologies has increased the scalability of this strategy [ 29 ]. Indeed, carrier-free is an ideal drug deliver platform. These approaches of minimizing carriers are pivotal in addressing the limitations of current nanoscale delivery platforms, particularly concerning aspects such as loading capacity and toxicity [ 30 , 31 ]. Against this backdrop, strategies aimed at minimizing carriers are expected to be employed in the development of nanopesticides and offer potential solutions to current agriculture challenges. In recent years, some agricultural chemists have put forth substantial technological methods aimed at minimizing non-therapeutic carriers in nanopesticides. However, there is a notable lack of a systematic overview of this developmental direction, which is essential to provide comprehensive guidance for the creation of the new generation of nanopesticides.

In this review, we first summarize the development and characteristics of nanopesticides with minimizing carriers (NMC) prepared through prodrug design and molecular self-assembly, and compare them with nanopesticides employing non-therapeutic nanomaterials as carriers (NNC). Next, the development strategies and preparation mechanisms of recent research on NMC are analyzed, including reactions between small molecules, reactions between host–guest compounds and small molecules, and reactions between low molecular weight polymers and small molecules. Finally, challenges and opportunities for the future development of NMC are discussed based on current scientific research progress. We hope that this review effectively elucidates the significance of NMC development for nanopesticides and offers innovative ideas for the long-term green revolution of pesticide in the future.

2 Progress and Properties

As materials science and nanotechnology become integral to pesticide research, the past decade has witnessed rapid advancements in the realm of nanopesticides. In light of the observed trend in the number of published papers and the convergence of research fields, it can be anticipated that future investigations into nanopesticides will continue to thrive (Fig.  2 A). The emergence of the NNC system primarily stems from the utilization of nanotechnology in pesticide formulations, and the carrier role played by nanoparticles in pesticides. In contrast with conventional pesticide formulations plagued by issues such as high organic solvent content, poor dispersibility, and short duration of action, the NNC system has advantages in enhancing the physical and chemical properties, achieving targeted and sustained release, and multifunctionality [ 32 ]. Therefore, the related patented products of NNC systems have been successfully introduced to the market. Examples include products such as Nualgi Foliar Spray, Dedalo Elite, and AZteroid FC 3.3 [ 9 ]. In addition, the expanding production scale of EEMs aligns with the feasibility of large-scale application of NNC systems in the future [ 24 ]. Through data retrieval, it can be seen that most of research articles on nanopesticides are driven by the functional modification of nanocarriers or the composite use of multiple nanomaterials. The delivery of genetic material via nanomaterials has also started to garner attention in the realms of crop engineering and plant protection [ 33 , 34 ]. But researches on carrier-free nanopesticides are sparse. However, what cannot be ignored is the extensive research on molecular self-assembly and pesticide delivery during the development of nanopesticides [ 35 , 36 ]. Molecular self-assembly makes the transformation from molecular entities to micron- or nanoscale substances [ 37 ], which is also one of the key foundations of current nanomedicine for active molecules delivery [ 38 ]. NMC, as a nanopesticide, relies on minimal or negligible use of nanomaterials to form nanoparticles, microspheres, vesicles, or other delivery systems (the molecular weight of all compounds cited in this article does not exceed 10 k). Molecular self-assembly stands out as one of the pivotal steps for obtaining this system. Therefore, molecular self-assembly, which have gained significant ground in research of pesticide delivery, has the potential to contribute to the continued development of NMC.

figure 2

Development overview and comparison of properties of NMC and NNC. A Publication trends and research areas of NMC and NNC. Keyword search and paper collection source Web of Science, including only research papers. B A comparison of the loading capacity of NMC and NNC. Relevant information of cited references is in Table S1 of Supplementary Information. C A comparison of comprehensive properties of NMC and NNC. The evaluation criteria for the comprehensive properties of NMC and NNC based on the relevant data in Table S1 -2 of Supplementary Information. D The target organism toxicity of NMC and NNC. The lower and upper ends of the box represent the 25th and 75th percentiles, respectively, while the line and cross inside the box denote the median and mean, respectively. The whiskers indicate the 90th and 10th percentiles. These parameters are derived from dose–response relationships, such as EC 50 or LC 50 , which are inversely related to toxicity. Their inverse ratios are compared in the analysis. Relevant information of cited references is in Table S2-3 of Supplementary Information

NMC typically boasts high loading capacity and mitigates the risk of toxic events associated with excessive use of nanomaterials for loading enhancement [ 30 ]. Figure  2 B summarizes the loading capacity reported in recent studies of nanopesticides. The results indicated that, at comparable sizes, NMC exhibited significantly superior pesticide loading capacity compared to NNC, which encompassed SiO 2 , polymer, MOF, and their composites (Table S1 ). NNC employs these materials for pesticide loading through encapsulation, adsorption, or modification. In the NMC system, besides utilizing small molecule compounds, low molecular weight polymer can also be selected as one of the monomers participating in prodrug design and molecular self-assembly. For instance, polyethylenimine (PEI) molecules can be involved in the preparation of NMC system and can also serve as modified carriers in NNC system [ 39 ]. It is evident that the variances in preparation strategy and material choices between NMC and NNC systems directly result in essential difference in loading capacity between the two systems. For nanopesticides, the superior loading capacity exhibited by NMC delivery systems can play a crucial role in reducing the dose administered, offering a potential strategy to mitigate the development of pesticide resistance and improve safety [ 40 ].

When comparing the comprehensive performance of NNC and NMC (Fig.  2 C), toxicity and safety need to be mentioned first. In fact, the standout characteristic of nanopesticides is that nanonization strengthens biological effects, such as biological barrier penetration, adjustment of reactive oxygen species (ROS), and modulation of plant metabolism and signaling pathways [ 41 ]. In the analysis conducted by Kah et al. in 2018 [ 13 ], the toxicity of nanopesticides to target organisms increased by 24% compared to non-nanopesticides. Similarly, in the study by Wang et al. in 2022 [ 12 ], this increase was reported to be 31.5%. These analyses, focusing on EEMs and NNC as the primary research subject, have revealed an augmentation in the toxic effects of nanopesticides. However, additional multidimensional assessment criteria may be necessary for evaluating toxicity to non-target organisms, particularly concerning genotoxicity against refractory substances. At the same time, attention should be given to controversial experimental results regarding the safety assessment of aquatic life [ 42 ]. The very direct introduction of nanomaterials that are difficult to degrade naturally into organisms and ecosystems could be a double-edged sword. This is likely to be one of the primary constraints on market regulation of NNC-based nanopesticides in the future [ 43 ]. Herein, we also conducted a preliminary comparison of the target organism toxicity of NMC and NNC (Fig.  2 D and Table S2). The results indicate that the average value of target organism toxicity of NMC was 1.29 times that of NNC, suggesting that NMC may potentially offer efficacy advantages (Table S3). In terms of non-target organism toxicity, the water-only NMC system prepared by An et al. [ 44 ] showed low toxicity to non-target plant seeds, human epithelial cells, zebrafish, earthworms, and Escherichia coli . Furthermore, the presence of prodrugs may also enhance biosafety. These results indicate that pure NMC systems have the potential to mitigate the potential toxicity associated with organic solvents, surfactants, or nanomaterials. But due to the small sample size and the variability in biological test conditions, further studies are required for validation.

The functionality of nanopesticide systems currently includes basic loading and release functions as well as additional functions, such as nutritional functions and stress alleviation. The development of these functions mostly comes from the addition of exogenous compounds, so both NMC and NNC are easy to implement. Importantly, the stimulus-responsive capability of NMC can also be attributed to the reversibility of the structures formed through self-assembly, enabling NMC to response to environmental factors such as temperature and pH [ 45 , 46 ]. Another potential advantage of NMC is cost-effectiveness, mainly attributed to exclude large-scale manufacturing of carriers and the improvement of efficacy. However, the absence of a protective carrier leads to limited stability for NMC, potentially hindering its delivery in complex agricultural environments. Additionally, another drawback of NMC is accessibility. Its preparation requires careful consideration of the physical and chemical properties of the reacted monomer molecules, as well as the properties of the resulting combined prodrug molecules, rendering it more challenging than the NNC system. The formation of NMC necessitates the design of specific molecular structures, and detailed adjustments to reaction conditions are also required. Therefore, the next chapter summarizes current preparation strategies of NMC and analyzes design concepts for future reference.

3 Preparation Strategies

The design methodology of carrier-free nanodrugs in medicine can provide insightful references for NMC [ 28 ]. However, differences in application environments introduce variations in overall design considerations. While the concept of NMC is relatively new in the development of nanopesticides, several promising results have been reported. The studies primarily both innovated existing pesticide molecules through structural design to align with the conditions required for molecular self-assembly. For agricultural application, the preparation strategy of NMC is designed based on pesticide molecules, including between small molecules, between host–guest compounds and small molecules, and between low molecular polymers and small molecules. The resulting NMC exhibited response functions based on the specific target and the application scenario of the pesticide [ 47 ]. Additionally, enhancing the efficiency of pesticide application and minimizing the environmental toxicity of potent pesticides are also key considerations in the current design concepts for NMC [ 48 ].

3.1 NMC Formed Between Small Molecules

The molecular self-assembly is a bottom-up process, necessitating the aggregation of free small molecules for the formation of the nano-delivery system. However, it is difficult to rely solely on an ordinary pesticide molecule in establishing relatively stable nano-assembly systems. Therefore, it becomes necessary to construct prodrug conjugates with amphipathic properties. In addition to serving as the foundation for the formation of macroscopic nanoparticles, these prodrug conjugates typically exhibit more optimized physical and chemical properties [ 49 , 50 ]. For pesticide application, the specific objectives include achieving higher efficacy, minimizing environmental toxicity, and incorporating specific response functions. The following are the specific strategies for constructing prodrug conjugates through reactions between small molecules.

Some pesticide molecules with amino group can be bonded to small molecules, enabling the construction of prodrug conjugates [ 51 ]. Tian et al. [ 52 ] conjugated fipronil with three natural carboxylic acids of varying polarities, strategically modulating the intramolecular polar balancing forces of the conjugate to achieve nanospheres with optimal physical and chemical properties (Fig.  3 A). Simultaneously, the resulting amphipathic molecules enhanced affinity with the leaf surface, thereby reducing the surface tension of pesticide droplets and enhancing deposition efficiency. Additionally, the toxicity of zebrafish exposed to molecules incorporating long carbon chains and aromatic rings was reduced by nearly four times compared to fipronil. Also, utilizing the amino group on fipronil, Zhao et al. [ 53 ] introduced 2-sulfobenzaldehyde and facilitated its combination to create an imine covalent bond, subsequently self-assembling into nanomicelles with a diameter of approximately 16.9 nm. The dynamic nature of the imine construction enables the system to precisely release highly active fipronil under conditions of high humidity and weak alkalinity. Utilizing the amide bond-forming reaction, Zhang et al. [ 47 ] conjugated fluazinam with alkyl aliphatic acids of varying lengths (Fig.  3 B). The results indicated an inverse relationship between the degradation rate of the amide bond in papain and the length of the conjugated alkyl fatty acid, allowing for the customization of the enzyme-responsive NMC.

Esterification reactions can be employed to generate amphiphilic alkylated prodrug conjugates. Research by Liu et al. [ 54 ] showed that 2,4-dichlorophenoxyacetic acid or picloram can self-assemble in water to form nanoparticles with a liquid crystal structure after conjugation with phytantriol or glyceryl monooleate (Fig.  3 C). This nanoparticle with a liquid crystal structure is a promising pesticide delivery system in terms of its surfactant reduction for improved environmental safety [ 55 ]. In comparison with simple alkyl ester conjugates, amphiphilic conjugates reduced the loss of inverse cubic structure, addressing the issue of low pesticide loading in the original liquid crystal system. Enhancements in ester systems will contribute to the future advancement of nanopesticides featuring liquid crystal structures.

Two small molecules with specific structures can be constructed into self-assembling nanoparticles through noncovalent interactions. Tian et al. [ 48 ] employed berberine and curcumin, both possessing bactericidal effects extracted from medicinal plants, to undergo supramolecular self-assembly through various noncovalent interactions. This study introduces innovative approaches for creating NMC systems incorporating botanical pesticides. Based on nanoprecipitation method, Li et al. [ 40 ] regulated the solvent for precipitating myclobutanil, and during this precipitation process, tannic acid, possessing a noncovalent molecular structure, could interact with myclobutanil. The bound molecules persistently rotated and intertwined through noncovalent interactions, culminating in the formation of a spherical three-dimensional structure (Fig.  3 D). Tian et al. utilized the protonation of the tertiary amine group in spinosad to bind with sulfamic acid through noncovalent electrostatic interactions, subsequently undergoing winding and rotation to form a sphere (Fig.  3 E). Among them, temperature, pH, molar ratio, and ionic strength might have an impact on co-assembly of this system. In the research conducted by Cui et al. [ 56 ], nanoparticles were produced using emamectin benzoate and sodium lignosulfonate through electrostatic self-assembly. The research results indicate that the physical and chemical properties of NMC system can be optimized through the adjustment of surfactants.

figure 3

NMC preparation strategy based on the interaction between small molecules . A Schematic illustration of fipronil and three carboxylic acids forming NMC based on amide bond [ 52 ], copyright 2022, Elsevier. B Schematic illustration of fluazinam and three alkyl aliphatic acids forming NMC based on amide bond [ 47 ], copyright 2023, American Chemical Society. C Schematic illustration of 2,4-dichlorophenoxyacetic acid or picloraml and phytantriol or glyceryl monooleate forming NMC based on ester bond [ 54 ], copyright 2018, Elsevier. D Schematic illustration of myclobutanil and tannic acid forming NMC based on noncovalent interaction [ 40 ], copyright 2023, Wiley Online. E Schematic illustration of spinosad and sulfamic acid forming NMC based on noncovalent interaction [ 58 ], copyright 2021, Royal Society of Chemistry

In addition to the aforementioned preparation concepts, the co-crystallization strategy, rooted in the supramolecular self-assembly mechanism, is also a viable approach for developing NMC [ 57 ]. Significantly, NMC constructed with two pesticide molecules often exhibit synergistic effects, which requires further discussion in the future.

3.2 NMC Formed Between Host–Guest Compounds and Small Molecules

The development of NMC based on prodrug conjugates via host–guest interactions stands out as one of the currently effective preparation strategies. Water-soluble host molecules employ the hydrophobic effect of the cavity to facilitate host–guest self-assembly with pesticide molecules [ 59 ]. Commonly utilized host molecules encompass pillar[ n ]arenes, cucurbit[ n ]urils, and cyclodextrins.

Designing supramolecular polymers for the highly toxic pesticide paraquat holds great significance in enhancing safety and functionality [ 60 ]. In Fig.  4 A, based on the supramolecular chemistry of pillar[ n ]arenes, Chi et al. [ 46 ] presented a preparation method for NMC with dual-thermoresponsiveness. In their study, pillar[ 10 ]arene and paraquat derivatives formed a 1:2 [ 3 ] pseudorotaxane, which can self-assemble into vesicles in water above the lower critical solution temperature (LCST) of paraquat derivatives. Leveraging the different LCST behaviors of pillar[ 10 ]arene and poly(N-isopropylacrylamide) (the block where paraquat was introduced), dual-thermoresponsiveness was attained. Later, Song et al. [ 61 ] utilized pillar[ 5 ]arenes and benquitrione through selective dynamic self-assembly to create vesicles, which improved the spreading of pesticide droplets on the hydrophobic interface through host–guest and hydrogen bonding interactions.

figure 4

NMC preparation strategy based on the interaction between host–guest compounds and small molecules. A Schematic illustration of supramolecular complexes formed by host–guest interactions based on pillar[ 10 ]arenes [ 46 ], copyright 2016, American Chemical Society. B Schematic illustration of supramolecular complexes formed by host–guest interactions based on cucurbit[ 8 ]uril [ 63 ], copyright 2018, Springer Nature. C Schematic illustration of supramolecular complexes formed by host–guest interactions based on β -cyclodextrin [ 64 ], copyright 2023, Wiley Online

Cucurbit[ n ]urils are also macrocyclic molecules capable of encapsulating many guest molecules [ 62 ], and the tunable stimulus responsiveness of the resulting complexes has garnered widespread attention. To also enhance the safety of paraquat, Gao et al. [ 63 ] devised supramolecular vesicles through molecular self-assembly relying on cucurbit[ 8 ]uril. In Fig.  4 B, the researchers initially synthesized a hydrophobic azobenzene derivative ( Trans -G), then created an amphiphilic ternary complex involving paraquat, Trans -G, and cucurbit[ 8 ]uril in water. Finally, the complex formed hollow spheres through self-assembly, which also capable of loading active substances, and achieved responsive release under ultraviolet light through the trans -to- cis isomerization of Trans -G. In a recent study by Ji et al. [ 45 ], highly bioactive carbazole-modified amphiphilic quaternary ammonium salts with cationic N -benzylimidazolium pendants were prepared. Then, the host cucurbit[ 7 ]uril was introduced to construct a supramolecular system, regulating its release by the addition of competitive molecules (such as 1-adamantanamine hydrochloride).

Cyclodextrins, especially β -cyclodextrin, are recognized as ideal macrocyclic host molecules in the agricultural field due to their good physical and chemical properties and cost-effectiveness. In Yang et al.’s study [ 64 ], azobenzene analogs featuring the pharmacophore-isopropanolamine moiety were designed as guest molecules in β -cyclodextrin due to their photoresponsive property and antibacterial function (Fig.  4 C). This light-responsive antibacterial system formed through supramolecular self-assembly, which can inhibit up to 55.84% against rice bacterial blight pathogens by UV–Vis exposure. Importantly, it has been demonstrated to be non-toxic to various non-target organisms (plant, aquatic organism, and human cell lines). Also based on the host–guest interaction of β -cyclodextrin, Ji et al. [ 65 ] synthesized adamantane-decorated 1,3,4-oxadiazoles to enhance the formation of antibacterial supramolecular complexes. After the host–guest assembly was formed, the water solubility and foliar surface wettability were significantly improved and improved the control effect against rice bacterial blight and kiwi canker diseases.

3.3 NMC Formed Between Low Molecular Weight Polymers and Small Molecules

The utilization of low molecular weight polymers and small molecules to create nanoassemblies is a distinctive strategy for NMC preparation, which is different from the large use of high polymers simply as carriers. Low molecular weight polymers lack molecular entanglement and have shorter chain segments, leading to faster degradation in nature. Higher molecular mobility facilitates participation in the molecular self-assembly of the solution system. Conjugating small molecules to these polymers alters the water solubility, safety, and dispersion of NMC while maintaining a higher loading capacity [ 28 ].

In the previous studies, Tang et al. [ 66 ] employed cinnamaldehyde and branched PEI of varying molecular weights to create Schiff base complexes, which subsequently self-assembled into nanoparticles through noncovalent interactions (Fig.  5 A). The release of this NMC with Schiff base intelligently responds to the acidic biological microenvironment created by some fungal pathogens during infection. In another study by Tang et al. [ 67 ], it was observed that cycloheximide and polyhexamethylene biguanide self-assemble in aqueous solution to form nanospheres (Fig.  5 B). The process of self-assembly is governed by the electrostatic attraction between the anions of fenhexamid and the skeleton of polyhexamethylene biguanide, as well as the hydrophobic interaction force induced by the anions of fenhexamid. In Fig.  5 C, Wang et al. [ 68 ] synthesized amphiphilic complexes capable of self-assembly into nanoparticles in water. Subsequently, poly(salicylic acid) attracted acifluorfen to interact with it through noncovalent interactions, including hydrogen bonding and π − π stacking, ultimately resulting in the formation of co-assembled nanoparticles. The results indicated that stable co-assemblies tend to form when there was a balance between attractive and electrostatic repulsive forces between polymers and small molecules.

figure 5

NMC preparation strategy based on the interaction between low molecular weight polymers and small molecules. A Schematic illustration of supramolecular complexes formed by PEI and cinnamaldehyde based on Schiff base [ 66 ], copyright 2023, Elsevier. B Schematic illustration of supramolecular complexes formed by polyhexamethylene biguanide and fenhexamid based on noncovalent interaction [ 67 ], copyright 2021, Royal Society of Chemistry. C Schematic illustration of supramolecular complexes formed by poly(salicylic acid) and acifluorfen based on noncovalent interaction [ 68 ], copyright 2023, American Chemical Society. D Schematic illustration of possible acting forces driving the formation of the self-assembly between low molecular weight polymers and small molecules [ 69 ], copyright 2022, American Chemical Society

In the co-assembled between polymers and small molecules to form NMC, the average molecular weight of the polymer often plays a crucial role. For example, branched PEI with a lower average molecular weight cannot form a strong interaction with 2,4-dichlorophenoxyacetic acid. As the average molecular weight increases, its longer main chain exhibited various forces that drive it to entangle with each other, forming a three-dimensional structure (Fig.  5 D). However, this does not imply that infinitely increasing the length of the main chain will form better co-assembly. Excessively long main chains may hinder rotational winding. When designing future NMC systems, the suitable average molecular weight of the selected polymer can be further determined by analyzing the appearance, pH value, and conductivity changes of the reactants [ 69 ]. In addition, the development of supramolecular biopolymers can also expand ideas for the preparation of this type of NMC [ 11 ].

4 Conclusions and Perspectives

Currently, the United Nations has incorporated the reduction the input of agrochemicals harmful to the environment and human health as one of the Sustainable Development Goals. Despite the emergence of nanopesticides as environmentally friendly alternatives to traditional pesticides, the excessive introduction of non-therapeutic or functional nanomaterials of certain research or products may pose risks to the environment and human safety. Critically, this thought has the potential to lead future research in misguided directions. Therefore, a more nuanced and comprehensive understanding are needed to discern the true benefits of extensively used nanomaterials in agrochemicals. Herein, we propose NMC that have the potential to become hot research topics. Based on the current research progress, it can be anticipated that NMC will realize widespread applications as a promising nanopesticide in the future. The significant advantages of NMC through molecular self-assembly are the preparation process that does not require excessive energy input, the extremely high loading capacity, and rich functionalization potential. However, further development is needed for NMC to attain full industrialization in the future (Fig.  6 ).

figure 6

Potential directions for future research on NMC

In terms of preparation of NMC systems, the prodrug design and molecular self-assembly stands are crucial steps, the monitoring and prediction of these reactions are necessary. Accurate quantification of the molecular structure of prodrug molecules using machine learning algorithms to predict nanoparticle formation represents a promising method to implement these steps [ 70 ]. Molecular dynamics simulations can further elucidate the formation processes of prodrug molecule and self-assembled nanoparticles, while molecular docking can investigate the molecular interactions in this process in detail [ 71 ]. These technologies are anticipated to assist chemists in elucidating the kinetic mechanism of pesticide molecule self-assembly, directly benefiting the precise synthesis of NMC systems. Controlling the proportions of molecules involved in the reaction can maximize the loading efficiency, thereby minimizing pesticide resistance in pests and bacterial caused by multiple applications. Another important significance of this study is to elucidate the synergistic effects and regulatory mechanisms between different pesticide assembly molecules. This is a field that still lacks comprehensive understanding. Establishing a more extensive portfolio of self-assembled pesticide molecules is also a research agenda that requires a significant investment of time and resources. Artificial intelligence can help reduce the cost of actual experimental operations to accelerate the development of NMC [ 72 ].

Another focus is on the performance of the NMC system. Although the developed NMC exhibit good responsive release capabilities, it remains necessary to enhance the targeting ability of NMC toward pests and fungal, bacterial, and viral diseases. With the advancement of double-stranded RNA (dsRNA) that can silence genes for plant protection, there is a growing focus on developing nano-delivery platforms to enhance the uptake efficiency of exogenous RNA by targets [ 73 ]. It is crucial to develop targeting systems capable of promoting the translocation of dsRNA across cell membranes or penetrating plant cell walls. For example, Itzhakov et al. [ 74 ] recently suggested that incorporating capryl substituents enhances the membrane penetration capability of the delivery platform. While long carbon chain molecules have been utilized in constructing NMC prodrug molecules, further discussion is needed regarding their biofilm penetration properties. The next important concept to mention is the design of prodrug molecules, which contribute to enhancing the biosafety and microenvironmental response capabilities of the NMC system [ 47 ]. Prodrugs are highly valued in medicine, especially in tumor treatment, for their ability to respond to the microenvironment in the body. And similarly, the prodrug requires further design and development based on the microenvironment when plants are exposed to various biotic or abiotic stresses [ 75 ]. It is important to note that these entirely new chemical molecules might need to undergo a comprehensive safety assessment and registration process.

The size effect has always been the motivation for the ongoing development of nanopesticides, and NMC, utilizing a bottom-up self-assembly process, facilitate the creation of an extremely small delivery platform. Based on NMC nano-platform, a systematic investigation of the interaction between it and plant cell walls will contribute to unraveling the biological mechanism of nanosystems constructed from pure pesticide molecules [ 76 ]. The loading and activity of pesticide molecules in NMC systems significantly surpasses that of NNC, which might have different effects upon contact with plant cell walls [ 77 ], and this research is obviously lacking.

Manipulating the morphology and geometry of self-assembled systems presents another promising avenue for performance exploration [ 78 ]. The favorable characteristics exhibited by single-walled carbon nanotubes in plant delivery demonstrate that nano-delivery platforms with high aspect ratios may be more readily accepted by plant cells [ 79 ]. From this perspective, the incorporation of self-assembled nanofibers or nanorods into the NMC system is anticipated to enhance its application prospects in controlling plant diseases. Alterations in the morphology and geometry of nanoparticles can also influence their overall stability. Then, the critical aspect to emphasize here is the storage stability of NMC, which is extremely important for the development of industrialized pesticide formulations. Considering the inherent instability of self-assembly systems, ongoing research primarily concentrates on regulating the solvent environment and feeding parameters during their formation. The longer-term storage stability of NMC remains insufficiently scientifically evaluated, requiring comprehensive studies across different temperature storage conditions and transportation processes.

The final consideration involves the practical production of NMC, encompassing discussions on prodrug preparation and molecular self-assembly processes. It is crucial to emphasize that the intelligent design and high-throughput synthesis of prodrug molecules are critical issues that must be addressed to achieve the industrialization of NMC. The recently suggested large-scale self-assembly approach can also serve as references for the scaled-up production of NMC [ 80 , 81 ]. The effective execution of these strategies often necessitates the backing of dedicated production lines and equipment, thereby overcoming the limitations of traditional nanoprecipitation methods in terms of scalability. Microfluidic technology [ 62 ] and flash nanoprecipitation [ 82 ] methods can advance the progress of sophisticated, high-throughput, continuous-flow prodrug synthesis and molecular self-assembly. It is noteworthy that, given the necessity for cost-effective agricultural production, the optimization of NMC methods and engineering is imperative. The future emphasis will be on developing affordable production equipment of NMC system suitable for agricultural enterprises, with the possibility of downstream manipulation [ 83 ]. Additionally, future research should focus on environmentally friendly solvents that facilitate large-scale production, as the formation and overall performance of the NMC system are closely tied to the choice of solvent [ 84 ].

In summary, the development of NMC is expected to provide a new way for the future development of nanopesticides. Based on molecular structure design, NMC systems can be constructed via molecular self-assembly, which have high loading capacity, potentially high activity, good functionality, and industrialization prospects. The widespread use of NMC could help alleviate concerns regarding human health and environmental safety associated with the large-scale introduction of nanomaterials. Our perspective acknowledges that while certain NMC research has proposed viable design strategies and demonstrated promising developmental potential, addressing the remaining substantial research space and challenges in the future is crucial.

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This work was funded by the National Key Research Development Program of China (2022YFD1700500) and Beijing Natural Science Foundation (6232033).

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Wenjie Shangguan, Qiliang Huang, Huiping Chen, Yingying Zheng, Pengyue Zhao, Chong Cao, Manli Yu & Lidong Cao

College of Plant Protection, China Agricultural University, Beijing, 100193, People’s Republic of China

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WS and LC conceived the work. WS, YC, and LC organized the content and prepared the draft manuscript. WS, HC, and YZ typeset and created figures. QH, YC, and LC supervised the work. PZ, CC, and MY revised the manuscript. All authors contributed to the writing and revision of the manuscript.

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Shangguan, W., Huang, Q., Chen, H. et al. Making the Complicated Simple: A Minimizing Carrier Strategy on Innovative Nanopesticides. Nano-Micro Lett. 16 , 193 (2024).

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Spotlight on Nanotechnology: the African Continent

Nanoscience Teaching and Research program in South Africa Provisionally Accepted

  • 1 University of the Western Cape, South Africa
  • 2 Université de Lorraine, France

The final, formatted version of the article will be published soon.

Since 2012, the National Nanoscience Teaching and Training Platform (NNPTTP), funded by the South African Department of Science and Innovation (DSI), has been responsible for overseeing Africa's first-ever master's in nanoscience program. For over a decade, the NNPTTP has seen the cooperation of four partner universities across South Africa, namely the University of Johannesburg (UJ), University of the Free State (UFS), University of the Western Cape (UWC), and Nelson Mandela University (NMU), culminating in over 250 graduates trained in either nanophysics, nanochemistry, or nanobiology. Originally established to train professionals for a nanotechnologybased industry, both in South Africa and internationally, the program and platform has evolved into a testament to scientific collaboration. This paper discusses the program's framework, successes and challenges, related research, and future plans.

Keywords: nanoscience, Nanotechnology, nanophysics, Nanochemistry, nanobiology, Entrepreneurship

Received: 15 Mar 2024; Accepted: 15 May 2024.

Copyright: © 2024 Lindsay and Nel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Robert Lindsay, University of the Western Cape, Bellville, South Africa

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Researcher celebrated for valuable contributions in nanotechnology

Dr. Ajeet Kaushik

Dr. Ajeet Kaushik, assistant professor of chemistry at Florida Polytechnic University, is a highly respected speaker at international scientific events focusing on nanotechnology and biosensors.

Dr. Ajeet Kaushik’s expertise in nanotechnology, sensors, biosensors, and nanomedicine for health and environmental management has carried his stellar reputation across the country and around the world.

The assistant professor of chemistry at Florida Polytechnic University spent much of the 2023-2024 academic year sharing his knowledge both in the classroom and among his vaunted peers.

“Doing research in a particular field is not simple, and I have not done it alone. I have worked with many other researchers and students have assisted me as well,” Kaushik said. “Whenever my work is recognized, they are part of that recognition.”

Among his international recognitions was being invited by the government of India’s Ministry of Education to participate in its December 2023 Global Initiative of Academic Networks’ ( GIAN ) five-day workshop course at the Guru Jambheshwar University of Science and Technology in Hisar, a city in northwestern India. Kaushik served as a foreign expert for the course on biomedical nanotechnology for personalized health management. 

Although he focused on educating about how sensors, sensing technology, and nanomedicine can be optimized and transformed for better health quality, Kaushik said engaging with students was equally exciting.

“I tell them about Florida Poly, the wonderful work we do here, and our rankings,” Kaushik said. “Many of the senior students said they would want to come to the Florida Poly as visiting scholars for short-term or long-term experiences.” 

In April, Kaushik also was a keynote speaker at NanoFlorida 2024 in Tallahassee, Florida. This annual student-focused conference that brings together leading researchers, scientists, faculty, industry representatives, and companies in the name of nanoscience, nanoengineering, and nanotechnology. During the event, Florida Poly students, Justin Sanchez-Almirola, Alexander Gage, and Riley Orr, presented their research and received undergraduate research appreciation awards. 

In late 2023, Kaushik was named to Stanford University’s list of the world’s top 2% of scientists for the third consecutive year. The list recognizes those scientists who actively publish their work, and is based on the number of articles published by the researchers and the citations their papers receive.

Kaushik has over 280 technical papers, 10 edited books, and three granted U.S. patents. He also held more than 10 editorial positions at respected journals and was a faculty-elected member of Florida Poly’s Board of Trustees for the 2023-2024 academic year.

“I am happy to have important knowledge and grateful to be able to share it with others,” he said. “I feel thankful and blessed to be able to do so at Florida Poly and I appreciate the help and support of the institution’s leadership.”

Contact: Lydia Guzmán Director of Communications 863-874-8557

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Nanotechnology refers to engineered structures, devices, and systems. It is the manipulation of matter on a near-atomic scale to produce new structures, materials and devices. Nanomaterials have a length scale between 1 and 100 nanometers. At this size, materials begin to exhibit unique properties that affect physical, chemical, and biological behavior. Researching, developing, and utilizing these properties is at the heart of new technology.

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Workers within nanotechnology-related industries may be exposed to uniquely engineered materials. This includes materials with new sizes, shapes, and physical and chemical properties. Occupational health risks associated with manufacturing and using nanomaterials are not yet clearly understood. More research is needed to understand the impact of nanotechnology on health, and to determine appropriate exposure monitoring and control strategies.

At this time, the limited evidence available suggests caution when potential exposures to free–unbound nanoparticles may occur.

What is Known?

Studies have indicated that low solubility nanoparticles are more toxic than larger particles on a mass for mass basis. Particle surface area and surface chemistry are strong indicators for observed responses in cell cultures and animals. Studies suggests that some nanoparticles can move from the respiratory system to other organs. Research is continuing to understand how these unique properties may lead to specific health effects.

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Four from MIT named 2024 Knight-Hennessy Scholars

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MIT senior Owen Dugan, graduate student Vittorio Colicci ’22, predoctoral research fellow Carine You ’22, and recent alumna Carina Letong Hong ’22 are recipients of this year’s Knight-Hennessy Scholarships. The competitive fellowship, now in its seventh year, funds up to three years of graduate studies in any field at Stanford University. To date, 22 MIT students and alumni have been awarded Knight-Hennessy Scholarships.

“We are excited for these students to continue their education at Stanford with the generous support of the Knight Hennessy Scholarship,” says Kim Benard, associate dean of distinguished fellowships in Career Advising and Professional Development. “They have all demonstrated extraordinary dedication, intellect, and leadership, and this opportunity will allow them to further hone their skills to make real-world change.”

Vittorio Colicci ’22

Vittorio Colicci, from Trumbull, Connecticut, graduated from MIT in May 2022 with a BS in aerospace engineering and physics. He will receive his master’s degree in planetary sciences this spring. At Stanford, Colicci will pursue a PhD in earth and planetary sciences at the Stanford Doerr School of Sustainability. He hopes to investigate how surface processes on Earth and Mars have evolved through time alongside changes in habitability. Colicci has worked largely on spacecraft engineering projects, developing a monodisperse silica ceramic for electrospray thrusters and fabricating high-energy diffraction gratings for space telescopes. As a Presidential Graduate Fellow at MIT, he examined the influence of root geometry on soil cohesion for early terrestrial plants using 3D-printed reconstructions. Outside of research, Colicci served as co-director of TEDxMIT and propulsion lead for the MIT Rocket Team. He is also passionate about STEM engagement and outreach, having taught educational workshops in Zambia and India.

Owen Dugan, from Sleepy Hollow, New York, is a senior majoring in physics. As a Knight-Hennessy Scholar, he will pursue a PhD in computer science at the Stanford School of Engineering. Dugan aspires to combine artificial intelligence and physics, developing AI that enables breakthroughs in physics and using physics techniques to design more capable and safe AI systems. He has collaborated with researchers from Harvard University, the University of Chicago, and DeepMind, and has presented his first-author research at venues including the International Conference on Machine Learning, the MIT Mechanistic Interpretability Conference, and the American Physical Society March Meeting. Among other awards, Dugan is a Hertz Finalist, a U.S. Presidential Scholar, an MIT Outstanding Undergraduate Research Awardee, a Research Science Institute Scholar, and a Neo Scholar. He is also a co-founder of VeriLens, a funded startup enabling trust on the internet by cryptographically verifying digital media.

Carina Letong Hong ’22

Carina Letong Hong, from Canton, China, is currently pursuing a JD/PhD in mathematics at Stanford. A first-generation college student, Hong graduated from MIT in May 2022 with a double major in mathematics and physics and was inducted into Sigma Pi Sigma, the physics honor society. She then earned a neuroscience master’s degree with dissertation distinctions from the University of Oxford, where she conducted artificial intelligence and machine learning research at Sainsbury Wellcome Center’s Gatsby Unit. At Stanford Law School, Hong provides legal aid to low-income workers and uses economic analysis to push for law enforcement reform. She has published numerous papers in peer-reviewed journals, served as an expert referee for journals and conferences, and spoken at summits in the United States, Germany, France, the U.K., and China. She was the recipient of the AMS-MAA-SIAM Morgan Prize for Outstanding Research, the highest honor for an undergraduate in mathematics in North America; the AWM Alice T. Schafer Prize for Mathematical Excellence, given annually to an undergraduate woman in the United States; the Maryam Mirzakhani Fellowship; and a Rhodes Scholarship.

Carine You ’22

Carine You, from San Diego, California, graduated from MIT in May 2022 with bachelor’s degrees in electrical engineering and computer science and in mathematics. Since graduating, You has worked as a predoctoral research assistant with Professor Amy Finkelstein in the MIT Department of Economics, where she has studied the quality of Medicare nursing home care and the targeting of medical screening technologies. This fall, You will embark on a PhD in economic analysis and policy at the Stanford Graduate School of Business. She wishes to address pressing issues in environmental and health-care markets, with a particular focus on economic efficiency and equity. You previously developed audio signal processing algorithms at Bose, refined mechanistic models to inform respiratory monitoring at the MIT Research Laboratory of Electronics, and analyzed corruption in developmental projects in India at the World Bank. Through Middle East Entrepreneurs of Tomorrow, she taught computer science to Israeli and Palestinian students in Jerusalem and spearheaded an online pilot expansion for the organization. At MIT, she was named a Burchard Scholar.

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U.S. Tightens Rules on Risky Virus Research

A long-awaited new policy broadens the type of regulated viruses, bacteria, fungi and toxins, including those that could threaten crops and livestock.

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By Carl Zimmer and Benjamin Mueller

The White House has unveiled tighter rules for research on potentially dangerous microbes and toxins, in an effort to stave off laboratory accidents that could unleash a pandemic.

The new policy, published Monday evening, arrives after years of deliberations by an expert panel and a charged public debate over whether Covid arose from an animal market or a laboratory in China.

A number of researchers worried that the government had been too lax about lab safety in the past, with some even calling for the creation of an independent agency to make decisions about risky experiments that could allow viruses, bacteria or fungi to spread quickly between people or become more deadly. But others warned against creating restrictive rules that would stifle valuable research without making people safer.

The debate grew sharper during the pandemic, as politicians raised questions about the origin of Covid. Those who suggested it came from a lab raised concerns about studies that tweaked pathogens to make them more dangerous — sometimes known as “gain of function” research.

The new policy, which applies to research funded by the federal government, strengthens the government’s oversight by replacing a short list of dangerous pathogens with broad categories into which more pathogens might fall. The policy pays attention not only to human pathogens, but also those that could threaten crops and livestock. And it provides more details about the kinds of experiments that would draw the attention of government regulators.

The rules will take effect in a year, giving government agencies and departments time to update their guidance to meet the new requirements.

“It’s a big and important step forward,” said Dr. Tom Inglesby, the director of the Johns Hopkins Center for Health Security and a longtime proponent of stricter safety regulations. “I think this policy is what any reasonable member of the public would expect is in place in terms of oversight of the world’s most transmissible and lethal organisms.”

Still, the policy does not embrace the most aggressive proposals made by lab safety proponents, such as creating an independent regulatory agency. It also makes exemptions for certain types of research, including disease surveillance and vaccine development. And some parts of the policy are recommendations rather than government-enforced requirements.

“It’s a moderate shift in policy, with a number of more significant signals about how the White House expects the issue to be treated moving forward,” said Nicholas Evans, an ethicist at University of Massachusetts Lowell.

Experts have been waiting for the policy for more than a year. Still, some said they were surprised that it came out at such a politically fraught moment . “I wasn’t expecting anything, especially in an election year,” Dr. Evans said. “I’m pleasantly surprised.”

Under the new policy, scientists who want to carry out experiments will need to run their proposals past their universities or research institutions, which will to determine if the work poses a risk. Potentially dangerous proposals will then be reviewed by government agencies. The most scrutiny will go to experiments that could result in the most dangerous outcomes, such as those tweaking pathogens that could start a pandemic.

In a guidance document , the White House provided examples of research that would be expected to come under such scrutiny. In one case, they envisioned scientists trying to understand the evolutionary steps a pathogen needed to transmit more easily between humans. The researchers might try to produce a transmissible strain to study, for example, by repeatedly infecting human cells in petri dishes, allowing the pathogens to evolve more efficient ways to enter the cells.

Scientists who do not follow the new policy could become ineligible for federal funding for their work. Their entire institution may have its support for life science research cut off as well.

One of the weaknesses of existing policies is that they only apply to funding given out by the federal government. But for years , the National Institutes of Health and other government agencies have struggled with stagnant funding, leading some researchers to turn instead to private sources. In recent years, for example, crypto titans have poured money into pandemic prevention research.

The new policy does not give the government direct regulation of privately funded research. But it does say that research institutions that receive any federal money for life-science research should apply a similar oversight to scientists doing research with support from outside the government.

“This effectively limits them, as the N.I.H. does a lot of work everywhere in the world,” Dr. Evans said.

The new policy takes into account the advances in biotechnology that could lead to new risks. When pathogens become extinct, for example, they can be resurrected by recreating their genomes. Research on extinct pathogens will draw the highest levels of scrutiny.

Dr. Evans also noted that the new rules emphasize the risk that lab research can have on plants and animals. In the 20th century, the United States and Russia both carried out extensive research on crop-destroying pathogens such as wheat-killing fungi as part of their biological weapons programs. “It’s significant as a signal the White House is sending,” Dr. Evans said.

Marc Lipsitch, an epidemiologist at Harvard and a longtime critic of the government’s policy, gave the new one a grade of A minus. “I think it’s a lot clearer and more specific in many ways than the old guidance,” he said. But he was disappointed that the government will not provide detailed information to the public about the risky research it evaluates. “The transparency is far from transparent,” he said.

Scientists who have warned of the dangers of impeding useful virus research were also largely optimistic about the new rules.

Gigi Gronvall, a biosafety specialist at the Johns Hopkins Bloomberg School of Public Health, said the policy’s success would depend on how federal health officials interpreted it, but applauded the way it recognized the value of research needed during a crisis, such as the current bird flu outbreak .

“I was cautiously optimistic in reading through it,” she said of the policy. “It seems like the orientation is for it to be thoughtfully implemented so it doesn’t have a chilling effect on needed research.”

Anice Lowen, an influenza virologist at Emory University, said the expanded scope of the new policy was “reasonable.” She said, for instance, that the decision not to create an entirely new review body helped to alleviate concerns about how unwieldy the process might become.

Still, she said, ambiguities in the instructions for assessing risks in certain experiments made it difficult to know how different university and health officials would police them.

“I think there will be more reviews carried out, and more research will be slowed down because of it,” she said.

Carl Zimmer covers news about science for The Times and writes the Origins column . More about Carl Zimmer

Benjamin Mueller reports on health and medicine. He was previously a U.K. correspondent in London and a police reporter in New York. More about Benjamin Mueller

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Emerging Applications of Nanotechnology in Healthcare Systems: Grand Challenges and Perspectives

Sumaira anjum.

1 Department of Biotechnology, Kinnaird College for Women, Lahore 54000, Pakistan; moc.liamg@711euqahsiaras (S.I.); moc.liamg@31amitafh (H.F.); moc.liamg@39qoorafahijaw (W.F.); [email protected] (I.A.)

Sara Ishaque

Hijab fatima, wajiha farooq, christophe hano.

2 Laboratoire de Biologie des Ligneux et des Grandes Cultures (LBLGC), INRAe USC1328, Université d’Orléans, 28000 Chartres, France; rf.snaelro-vinu@onah

Bilal Haider Abbasi

3 Department of Biotechnology, Quaid-i-Azam University, Islamabad 54000, Pakistan; kp.ude.uaq@isabbahb

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Healthcare, as a basic human right, has often become the focus of the development of innovative technologies. Technological progress has significantly contributed to the provision of high-quality, on-time, acceptable, and affordable healthcare. Advancements in nanoscience have led to the emergence of a new generation of nanostructures. Each of them has a unique set of properties that account for their astonishing applications. Since its inception, nanotechnology has continuously affected healthcare and has exerted a tremendous influence on its transformation, contributing to better outcomes. In the last two decades, the world has seen nanotechnology taking steps towards its omnipresence and the process has been accelerated by extensive research in various healthcare sectors. The inclusion of nanotechnology and its allied nanocarriers/nanosystems in medicine is known as nanomedicine, a field that has brought about numerous benefits in disease prevention, diagnosis, and treatment. Various nanosystems have been found to be better candidates for theranostic purposes, in contrast to conventional ones. This review paper will shed light on medically significant nanosystems, as well as their applications and limitations in areas such as gene therapy, targeted drug delivery, and in the treatment of cancer and various genetic diseases. Although nanotechnology holds immense potential, it is yet to be exploited. More efforts need to be directed to overcome these limitations and make full use of its potential in order to revolutionize the healthcare sector in near future.

1. Introduction

Nanobiotechnology, a recently coined term, emerged from the blending of molecular biology and nanotechnology. It is a branch of science which revolves around structures or functional materials at the nanoscale, which are produced by employing both physical and chemical methods [ 1 ]. In the last thirty years, the discipline of nanotechnology has been a crucial area of research, due to the unique chemical, electrical, optical, biological, and magnetic properties of nanomaterials [ 2 ]. Nanotechnology has managed to attract a lot of attention, because it is an established fact that when nanotechnology joins hands with biotechnology, they give birth to a platform which holds immense potential and importance with respect to diversity in applications [ 3 ]. Some of these applications include medical imaging, diagnostic kits, diagnostic assays, biological sensors, dentistry, sterilization of medical device surfaces, sunscreens, cosmetics, sports equipment, textiles, environmental cleanup, and gene inactivation [ 1 , 4 , 5 ]. The development of nanotechnology has provided mankind with some incredible tools that allow the delineation of processes to a degree which was considered to be next to impossible a few years ago [ 6 ].

Various types of nanoparticles (NPs), such as metal, metal oxide, semiconductor, organic, and inorganic NPs, have been synthesized in order to exploit their properties. They can be formed via different procedures such as conventional chemical production and green synthesis processes [ 7 ]. Associated with toxicity, cost and efficiency, chemically produced NPs pose many problems. Thus, because of their ease of production, low cost and toxicity, bio-inspired NPs hold an edge over traditionally produced NPs [ 8 ]. The high cost of raw materials, drug wastage, chemical and physical incompatibilities, clinical drug interactions, and the occurrence of side effects associated with the dose, are the vital limitations of conventional approaches [ 9 ].

Generally, NPs range in size from 1 to 100 nm but some exceptions also exist [ 10 ]. For example, in medicine, NPs range in size from 5 to 250 nm [ 11 ]. There are also some nanosystems that may exceed several micrometers in size, e.g., liposomes. The definition and classification of NPs are continuously evolving as this field is progressing day and night. Adapting the technical and translational information on nanomaterials and nanotechnology from the US National Nanotechnology Initiative and European Commission, the authors feel that it is imperative to mention that the upper size limit of NPs cannot be restricted to 100 nm [ 12 ]. In fact, some commercial nanomedicine products are greater than 100 nm, e.g., abraxane (130 nm) and Myocet (180 nm). Therefore, we can limit or specify the range of nanomaterials only on the basis of their sizes [ 11 ].

Exceptionally small sizes enable NPs and nanodevices to exhibit novel properties and functions. It should be kept in mind that the small size of NPs gives them another advantage, perhaps their main advantage, which is that they have a very high surface area-to-volume ratio. This may sound trivial but this property actually makes them more reliable and reproducible [ 13 ]. In addition, they show enhanced catalytic activity, chemical stability, and thermal conductivity and non-linear optical performance [ 3 ]. Various NPs can be developed into nanosystems via modifications in their shape, surface properties, and size to efficiently utilize them in the imaging, diagnosis, and treatment of serious diseases. Controlled released therapy can be provided by means of these functionalized nanomaterials which send drugs to particular sites or tissues [ 14 ]. In order to optimize and promote tissue and cell interaction, some factors, such as charge, size, the pattern of nanoscale medical molecules, and shape, need to be modulated and investigated [ 15 ].

Nanotechnology products have become increasingly useful in healthcare and have led to the advent of novel nanosystems for the diagnosis, imaging, and treatment of various diseases, such as cancer, as well as cardiovascular, ocular, and central nervous system-related diseases [ 16 , 17 , 18 ]. Nanomaterials integrate well into biomedical devices because most biological systems are also nanosized [ 5 ]. In the field of drug delivery, nanosystems offer the precise delivery of drugs to the target tissues or organs with a controlled release and enhanced retention time as compared to conventional techniques. Nano-liposomes are one of the best examples of the nanosystems currently developed for targeted drug delivery to treat various types of cancers and cardiovascular diseases [ 9 , 14 ]. Drug delivery to target tissue, good biocompatibility, and the control of drug flow in the bloodstream are the most significant reasons for the usage of nano-liposomes [ 9 ].

Advents in nanomedicines and nanodevices has inspired numerous researchers to look for alternative therapies, as the currently employed methods are limited in terms of earlier detection and treatments. The astonishing properties and applications of various nanomaterials and nanosystems have made them pervasive in the development of technologies to be implemented in the near future. The purpose of this review is to provide readers with information about the most recent applications of nanotechnology in various healthcare sectors in one place. Furthermore, we also critically discuss the limitations, challenges, and future prospects of nanotechnology in allied healthcare systems.

2. Nanosystems Used in Various Healthcare Sectors

Nanotechnology revolves around some common nanostructures, no matter what field or area of application is concerned. Some of the important ones are nanoparticles, carbon nanotubes, dendrimers, nanoprobes, quantum dots, nano-diamonds, and nanowires ( Table 1 ). Nanoparticles possess unique characteristics and their strikingly small size makes them able to cross microscopic pores and membranes easily. Nanoparticles are broadly classified into five categories, including metal, lipid, ceramic, polymeric, and semi-conductor NPs. Metal NPs are made out of metal precursors. These in particular have unique optoelectrical properties [ 19 ]. Ceramic NPs are inorganic and nonmetal NPs are found in amorphous, polycrystalline hollow and dense forms [ 20 ]. They are efficient catalysts and help in the photodegradation of dyes and imaging technologies [ 21 ]. Semiconductor NPs have properties of both metal and non-metal NPs; hence, they also find applications in numerous fields such as photo-optics and electronic devices [ 22 , 23 ]. Polymeric NPs are organic NPs, which are either matrix particles—that are generally solid which can adhere to molecules to be transported—or are encapsulated within the particle [ 24 ]. Lipid NPs contain moieties that are lipid in nature. These are usually spherical in shape and diameters range from 10 to 100 nm. They have a solid lipid core and lipophilic molecules can be transported easily.

Applications of various nanostructures in healthcare sectors.

Carbon nanotubes (CNT) are nanosized, seamless tubes made out of graphite sheets. They have open terminal parts that are closed by fullerene caps. They have the highest mechanical strength out of all natural materials. They are efficient absorbers of magnetic radiation, along with providing the efficient conduction of heat and having catalyzing properties. Their properties are dependent on their purity, length and diameter, special surface area, and amorphous carbon. Carbon nanotubes are included in the fullerene nanotube family and have a rather cylindrical configuration. CNTs also include buckyballs, which are spherical and cylindrical in shape [ 25 ]. CNTs are widely employed in modern healthcare systems because they have the potential to overcome hindrances that were previously impossible to address. They can cross partially permeable cell membranes very easily, using a mechanism that is still unclear. They can carry small organic drugs, proteins, peptides, nucleic acids, antibiotics, etc., to precise locations. These small molecules can be either covalently attached, adsorbed, or encapsulated in these CNTs [ 26 ]. They can carry protein less than 80 KDa that can be bound either covalently or non-covalently. These are taken up by cells via endocytosis. CNTs also have applications in X-ray imaging [ 27 ]. A CNT solution was placed in a laser infrared beam, which was able to heat CNTs up to 158 °F in 2 min. Cells containing CNTs are not destroyed by laser beams since they can absorb near-infrared waves. These lasers can effectively kill cancer cells [ 28 ].

Dendrimers are naturally biodegradable nanopolymers. They are macromolecular nanostructures having a 3D globular shape due to the presence of many branched layers. Their small size (1–10 nm), globular structure, and the fact that they can penetrate through cell membranes due to their lipophilic nature make them ideal systems for use in healthcare for gene and drug delivery purposes [ 28 , 29 , 30 ]. A dendrimer structure consists of three major components—the core made of an atom or a multifunctional molecule, repetitive branching units covalently bound to the core, and many functional groups present at the terminal of the branching units [ 31 , 32 ]. Dendrimers interact with drugs through physical and chemical interactions. The physical interactions (encapsulation of the drug) are due to the presence of empty internal cavities, which bind the drug molecules through hydrophobic interactions [ 33 , 34 , 35 ]. The chemical interactions occur either through electrostatic interactions (due to the presence of ionizable functional groups in dendrimers) or through covalent bonding [ 36 ]. For covalent binding, the dendrimer surface is first mixed with active moieties such as poly-ethylene glycol (PEG) or p-amino benzoic acid, etc. After this, the drugs can successfully conjugate with the dendrimers through covalent bonding [ 32 , 37 ].

Nano-diamonds (NDs) are nanostructures consisting of a single diamond crystal with carbon in the sp 3 configuration. Their particle size is approx. 4–5 nm. NDs are very hard and chemically inert and they have high thermal conductivity and bio-compatibility [ 38 ]. They have a tunable surface and a large surface area to which drugs and genes can easily conjugate. The fluorescence produced by NDs makes them useful as imaging probes for diagnostic purposes [ 39 , 40 ]. All these properties of NDs are actually due to the combined characteristics of diamonds and NPs [ 40 ]. The structure of NDs consists of two major components—(1) the inner diamond core, with carbon atoms in the sp 3 configuration; and (2) the outer graphitic shell (carbon atoms in the sp 2 configuration), with functional groups on the terminal of dangling bonds [ 41 ]. Techniques used for the synthesis of NDs include the detonation of explosives, high temperature, high pressure, and the chemical vapor deposition method [ 22 ].

Quantum dots are synthetic nanostructures ranging in size between 1.5–10 nm. their semi-conductor nature allows them to transport electrons. When UV light passes through them, the electrons in the QDs are excited, and when these excited electrons move back to their ground state, they emit light. QDs emit light of different colors depending upon their size [ 42 ]. QDs made from heavy metals such as cadmium are very toxic and carcinogenic; therefore, they cannot be widely used in the health sector. However, graphene and carbon QDs are safe and stable and have wide scope in the health sector [ 43 ].

Nanofilms consist of polymeric sheets with a large surface area and a thickness of relatively few nanometers (10–100 nm) [ 44 ]. Multiple oppositely charged layers are assembled together to form multilayered yet ultra-thin biofilms. Layers are deposited one by one for deposition. Various methods are used for the deposition of individual layers, including fluidic assembly, electromagnetic deposition, spin coating, and emersion [ 45 ].

Liposomes are spherical vesicles made up of one or more lipid bilayers with an aqueous compartment in between them [ 42 , 43 ]. They are found in a variety of sizes, starting from as small as a few nanometers, and can be as large as several micrometers [ 44 ]. They are capable of entrapping various substances, including hydrophilic and lipophilic agents. Therefore, they are also considered to be the most efficient drug delivery system. Another reason for this is because their composition is very similar to the cellular membranes found in the body, which helps with drug delivery in vitro. Their large size also enables them to deliver a high quantity of drugs [ 45 ]. The major domains of healthcare in which nanotechnology-mediated nanosystems are playing their positive role are summarized in Figure 1 .

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Schematic presentation of applications of various nanosystems in allied healthcare sectors.

3. Applications of Nanotechnology in Healthcare Sectors

3.1. role of nanotechnology in gene therapy.

Gene therapy is a procedure to replace a defective gene in the DNA (which is responsible for causing a disease) with a normal gene. The gene is usually inserted into the stem cells using a vector [ 64 ]. Stem cells have long life and a self-renewal ability; therefore, they are the most suitable targets for gene therapy [ 65 ]. The vector used should be highly specific and efficient in releasing the gene or genes of variable sizes. It should not be recognized as an antigen by the host immune system. The vector must have the ability to express the inserted gene throughout the life of that organism [ 66 , 67 ]. When the gene is correctly inserted into the cells, it inhibits and corrects the functions of the mutated gene and induces the normal functioning of cells [ 68 , 69 ].

Viral vectors have been used for years in gene therapy and are still being used. They can take over the host metabolic machinery for the synthesis of proteins that are coded by their DNA. Furthermore, their insertion in the host genome is very stable, and the transduced cells cause the long-term expression of the transgene. These are the properties that make them suitable for gene therapy [ 67 , 68 ]. Some common and efficient viral vectors include lentivirus, retroviruses, adenoviruses, etc. [ 67 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ]. However, there are many risks associated with the use of viral vectors. These include the generation of an immune response, inflammation, and the occurrence of off-target changes in the host body. If the virus triggers the immune response, it not only makes the therapy less efficient but when the same virus enters the body the second time (with the desired gene inserted into its DNA), a secondary immune response occurs, which would rapidly kill the virus, making it impossible to use the same virus for gene therapy [ 77 , 78 , 79 , 80 , 81 ]. Inflammation caused by viral vectors can sometimes be very dangerous, as reported in a recent study in which a leukemic patient died when given a high dosage of adenovirus for gene therapy [ 82 ]. Virus virulent genes are deleted prior to therapy, which also compromises the integration and infection ability of viral vectors. Insertional mutagenesis can be life-threatening too, because sometimes these viruses (mostly retroviruses) insert DNA into the tumor-suppressing gene or the oncogenes, activating them to cause tumors in the host body. The selection of appropriate viruses for different body cells is another difficulty in the field of gene therapy. Moreover, viruses can also go through genetic changes with the passage of time, which can lead to other complications in the body [ 83 ]. These are some major concerns relating to viral gene therapies, and therefore these methods are not encouraged, and the world is now moving towards the use of nanostructures for gene therapy.

Gene therapy using non-viral nanostructures is safe, as compared to therapy using viral vectors. They are also much less oncogenic and rarely trigger immune responses. Their preparation is much easier than that of viral vectors. There is no risk of virus recombination and no limit on the size of the gene to be loaded. NPs are one of the many nanostructures that are used for non-viral gene delivery. The presence of a positive charge, small size, and high surface-to-volume ratio enables them to penetrate deep into the membranes, thus making them ideal vectors for gene delivery [ 84 , 85 , 86 ]. The major nanosystems used in gene therapy are shown in Figure 2 .

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Graphical representation of various nanosystems used in gene therapy.

One of the ways in which gene therapy treats many diseases is through gene silencing. Various diseases, such as autoimmune disorders, cancers, and viral infections, can be treated by silencing the expression of genes [ 87 ]. RNA interference using small interfering RNA (siRNA) has been used for gene silencing. SiRNA is a 21–25 nucleotide long double-stranded RNA molecule. It forms a complex with RNA-induced silencing complex (RISC) in the cytoplasm and targets the directed complementary mRNA molecule, thus silencing its expression [ 88 , 89 ].

This technique can be very useful if the problem of their stable delivery into the cytosol (they become unstable in physiological fluids) and limited intracellular uptake are resolved [ 90 ]. This problem can be resolved by using some vector system. Viral vectors are very risky to use, as mentioned earlier. However, non-viral NPs have been used to overcome these limitations [ 91 ]. For example, one of the over-expressed proteins in cancer cells is the RhoA protein. Anti-RhoA siRNA was encapsulated in chitosan-coated polyisohexylcyanoacrylate (PIHCA) NPs. When these NPs were administered to mice infected with breast cancer, they showed 90% tumor inhibition with no toxic effects [ 92 ].

In rheumatoid arthritis, tumor necrosis factor-α (TNF-α) plays a role in the release of cytokines and thus causes chronic inflammation. A nanocomplex, thiolated glycol chitosan (TGC) polymer loaded with poly-siRNA, was targeted to TNF-α, which proved to be very efficient in curing rheumatoid arthritis. The inhibition in bone erosion and a reduction in inflammation was also observed in mice in that study [ 93 ]. These are just a few examples; there are several other studies in which nanostructure-based complexes have been effectively used to deliver siRNA, thus treating various diseases.

In another way, genetic materials (RNA, DNA, siRNA) can be encapsulated or conjugated with NPs for efficient gene delivery [ 84 , 94 , 95 , 96 ]. The most efficient way to attach genes with NPs is through the formation of DNA-NP complexes. These complexes are formed by means of the electrostatic bonding between them. For this, the surface charge on the NPs is made positive, which then binds strongly with negatively charged nucleic acids. Liposomal and polymeric and many other nanostructures use this mechanism of gene transfer [ 85 , 97 , 98 , 99 , 100 ]. The encapsulation of genetic material in NPs protects them from enzymatic digestion when they are targeted into the cells. It also protects them from phagocytosis by monocytes [ 94 ]. Due to the advantageous aspects of nano-based gene therapy, research is in process on large scale to develop new strategies for its implementation in the healthcare sector.

3.2. The Role of Nanotechnology in Targeted Drug Delivery

Nanovectors have great potential in target-specific drug delivery for the treatment of various diseases. Targeted drug delivery is important, especially if the solvents of hydrophobic drugs are toxic. If these solvents are released somewhere else other than the target cell, they may enter the blood stream or other body fluids and contaminate them. Nanostructures allow the continuous controlled release of drugs in desired amounts. Specific and localized drug delivery also reduces drug doses. The small size of NPs allows them to penetrate deep into the tumor cells, and thus they can be useful in improving cancer treatments [ 94 ].

The NPs used for drug delivery must contain some important components, including a particle core, an outer biocompatible protective layer and a linking molecule for increased bioactivity (it attaches the core of NPs to bioactive molecules because of the reactive compounds present at both of its ends). Nanovectors are modified before drug delivery and this modification includes coating with ligands such as peptides, folic acid, and antibodies. Ligands are attached to NPs so that they can bind specifically to targeted sites to enhance the specificity even more [ 16 , 95 , 101 , 102 , 103 , 104 , 105 , 106 ]. It is essential to attach more than one ligand because if only one ligand is attached, there is a possibility that it may bind to receptors present in places other than on the targeted site. In addition, tumor cells are usually overexpress, i.e., they have more than one type of surface receptor [ 17 ].

Since nanovectors possess unique properties and various modifications can be performed during drug loading, scientists are now moving towards the implement of nanotechnology-based nanosystems for efficient targeted drug delivery with the aim of curing various serious diseases. Some examples of targeted drug delivery using nanovectors are discussed in the following sections.

3.3. Treating Cardiovascular Diseases through Nanosystems

Cardiovascular diseases cause millions of deaths around the world [ 18 ]. Various treatments have improved the survival rate of patients with heart diseases but none of them has achieved complete cardiac regeneration, especially for patients after cardiac infarction [ 107 ]. Stem cell therapy can be used for therapeutic angiogenesis [ 108 ]. Introducing anti-apoptotic and pro-angiogenic genes into the genetically engineered stem cells can prolong their rate of survival and increase their paracrine secretion [ 109 , 110 ]. Viral vectors cannot be used to deliver genes to stem cells as they cannot carry large gene volumes and have immunogenic effects. Bio-compatible NPs are efficient in transferring genes to stem cells. Various nanostructures can be used for delivering genes to stem cells. Liposomes are one of the best contenders for gene delivery as they can prevent the non-specific binding of genes and protect them from degradation [ 111 , 112 ]. Polymers show improved specificity for targets and higher efficiency [ 113 ]. In one study, chitosan alginate NPs were used to deliver growth factors to placental cells. The continuous release of growth factors improved the functioning of cardiac tissues at the site of myocardial infarction [ 114 ]. NPs also have the potential for tracking and monitoring stem cells. Superparamagnetic iron oxide nanosystems (SPIONs) are made to enter the cells by attaching to cell surfaces. These cells are then internalized by endocytosis [ 115 ]. Quantum dots can also be used for monitoring the living cells for a long time [ 116 , 117 ].

Hypertension is a disease that gives rise to many problems, including myocardial infarction, heart failure, stroke, increased blood pressure, and damage to many body organs, including the eyes, kidney, brain, etc. [ 118 ]. Many antihypertensive drugs have been used to treat this, but various problems are associated with the use of these drugs, including their short half-life, low bioavailability, poor solubility in water, unwanted side effects, and many more. Targeted drug delivery using nanostems has been effectively performed in order to solve these problems [ 119 ]. Nanocarriers that have been used so far for treating hypertension include lipid carrier NPs, solid lipid NPs, polymeric NPs, liposomes, and nanoemulsions [ 120 ]. These are just a few examples, but nanotechnology has very promising applications in treating many other cardiovascular diseases through non-viral stem cell-based therapies. Further studies on the effects of nanovectors in the cardiovascular system of a living model need to be performed before they can be safely used in humans.

3.4. Nanotechnology in the Treatment of Ocular Diseases

The efficient delivery of drugs in the eye is an enormous challenge because of the presence of complex barriers and elimination mechanisms in the eye. The various barriers present include the tear film, the ocular surface epithelium, and the internal blood–aqueous and blood–retinal barriers. NPs are, however, able to overcome these barriers because of their small size and highly variable surface properties. They can efficiently transport the drug to the targeted site with no toxic effects. Most of the NPs are biodegradable, which means they do not require surgical removal after they have delivered the drug [ 121 , 122 ].

Anterior eye diseases, such as cataracts, conjunctives, keratitis, dry eye, corneal injury, etc., are usually treated using eye drops but the corneal barrier causes drugs to have poor bioavailability. However, nanosystems can increase the bioavailability by prolonging the retention time of the drug on the surface of the eye and improving the penetration of the drug [ 123 ]. On the other hand, posterior eye diseases in the choroid and retina include retinoblastoma, glaucoma, choroidal neovascularization, macular degeneration, and posterior uveitis. Eye drops are not usually effective in treating these diseases, so interocular injections are performed, which leads to many unwanted side effects [ 124 ]. However, nanosystems have improved the delivery of drugs to the posterior portion of eye and the various nanosystems used for this purpose include nanovesicles, nanoimplants, NPs, and hydrogels [ 123 ].

3.5. Nanotechnology in the Treatment of Brain Diseases

Brain diseases can be treated efficiently if we can overcome the issue of the blood–brain barrier (BBB). The BBB is a boundary between circulating blood and the neural tissues of the brain. The presence of the BBB is the major hurdle in the treatment of brain diseases because it does not allow the drugs to enter the central nervous system (CNS) and maintains homeostasis in the brain. Any disturbance to the BBB causes neuro-inflammatory and neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, etc., but even a damaged BBB does not allow drugs to enter the brain [ 125 , 126 ]. However, various types of NPs can cross the BBB and so can efficiently deliver drugs to damaged areas of the brain. NPs use organic and inorganic materials as a core to penetrate the BBB. Inorganic materials include silica, molybdenum, cerium, iron, and gold, whereas organic materials that can be used include PLA, PLGA, and trehalose. The distinct features by which NPs are able to treat neurodegenerative diseases are their small size, high drug loading ability, and efficient imaging performance (particularly for inorganic NPs). Some NPs themselves show some therapeutic efficacy, i.e., showing antioxidant properties, inhibiting Aβ aggregation, and reducing ROS levels [ 125 ].

NPs, when conjugated with ligands, show the best performance by interacting with BBB receptors at low density. NPs can adopt multiple pathways in order to cross the BBB [ 127 ]. The proposed pathways which NPs can use to cross the BBB are shown in Figure 3 . The main pathways include

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Schematic representation of the various proposed pathways by which NPs can cross the blood–brain barrier.

  • The paracellular pathway and passive transmembrane diffusion;
  • Transport proteins: carrier-mediated transport and efflux proteins;
  • Receptor-mediated transcytosis;
  • Adsorptive-mediated transcytosis.

Through any of these pathways, NPs can cross the BBB and can be taken in by the neurons or active astrocytes of the brain [ 127 , 128 ]. In receptor-, adsorptive-, and carrier-mediated penetration of NPs across the BBB, various ligands are involved, such as:

  • Ligands that can adsorb proteins from the bloodstream [ 129 ];
  • Ligands that can directly interact with BBB transporters or receptors [ 130 , 131 , 132 ];
  • Ligands that can increase the hydrophobicity and charge of NPs [ 133 ];
  • Ligands that can improve the circulation time of NPs in the blood [ 133 ].

The morphology and charge of NPs are also important in this case. Zwitterion and neutral NPs have a greater circulation time compared to positively and negatively charged NPs [ 134 , 135 ]. Overcoming the blood–brain barrier has enabled NPs to be used for the treatment of many diseases such as stroke, Alzheimer’s, and Parkinson’s disease, and many more, which are discussed below.

3.6. Role of Nanotechnology in Cancer Diagnosis and Treatment

Nanomedicine involves the implementation of nanotechnology in the treatment, screening, and diagnosis of various diseases, including cancer, and has the potential to revolutionize public and individual health [ 134 ]. In the formulation of various drugs for cancer treatment and in the discovery of cancer biomarkers, nanotechnology plays a vital role [ 136 , 137 ]. Through prediction, personalized therapy, diagnosis, medicine, and the prevention of cancer, it also contributes comprehensive techniques and worthy approaches against cancer [ 138 ].

3.6.1. The Utilization of Different Methods Involving Nanotechnology in Cancer Diagnosis

Obstacles in the early detection of different kinds of cancer are expected to be solved with the use of nanotubes, nanocantilevers, NP probes, and nanowire arrays [ 139 ]. Without the utilization of radioactive labeling or extrinsic fluorescent dyes, micro-cantilevers were used to determine single nucleotide polymorphisms in a 10-mer DNA target oligo-nucleotide [ 140 ]. Information about biomarkers related to the tumor microenvironment and the distribution, presence, and relative abundance of cancer signatures has been provided by probes with molecularly targeted recognition agents [ 139 ]. On the basis of fluorescence resonance energy transfer, nanoprobe systems have shown the potential to detect DNA mutations in tumor cells in clinical samples, as well as to detect the loss of DNA [ 141 ]. At the early stage of cancer, the expression of typical biological molecules has been detected using carbon nanotubes [ 142 ].

3.6.2. Different Methods Used for Cancer Treatment

To ease the intake of vehicles into target cells, a number of cancer-targeting ligands, such as growth factors or folate, cytokines and antibodies, have been used [ 143 ]. Through enhanced permeability and retention effects, caplostatin (TNP-470) was found to aggregate selectively in the tumor vessels, as well as halting the hyper-permeability of cancerous blood vessels [ 144 , 145 ]. By means of the EPR effect, NP-conjugated chemo-therapeutic substances—for example, angiogenic minute molecule inhibitor and doxorubicin—can enter into cancer cells, causing a growth inhibition and particular vascular shutdown [ 146 , 147 , 148 ]. By enhancing imaging and targeting cancer cells, oligonucleotides perform an important function. Furthermore, coupling them to metallic NPs, e.g., quantum dots and magnetic, ruby-eye doped, and gold nanoparticles, increases their related vasculature [ 149 , 150 , 151 , 152 ]. For the direct observation of circulating tumor cells in blood, a new SERS NP system was also introduced recently [ 153 ].

3.6.3. Targeting the Cancerous Micro-Environment

The arginine-aspartic acid-glycine motif has been found to display strong selectivity and affinity for the cell surface in many proteins; therefore, it is an appropriate ligand for therapeutic NPs targeting cancer [ 154 ]. In an inactive form as a pro-drug or nanoformulation, a drug that has a short half-life or that is extremely cytotoxic in circulation may now be controlled. Through tumor-specific molecules, these drugs are targeted at the tumor micro-environment. The tumor micro-environment eases its transformation to an active state upon arriving at its destination. By attacking both stroma and tumor cells, this tumor-activated nanoformulation therapy performs its function [ 155 ].

Consisting of a lower dose of chemotherapeutic medicines, metronomic therapy includes an administered schedule which lacks long periods of rest [ 156 , 157 ]. The novelty of this concept is in targeting the tumor micro-environment, specifically endothelial cells that are highly sensitive to the continual administration of low dosages of medicine as compared to cancerous cells. Thus, tumor angiogenesis is inhibited, causing the inhibition of tumor growth [ 158 ]. Poly-base NPs, upon aggregation in the low-P H micro-environment provided by the tumor tissue, become captured in the fenestrated cancerous vasculature and aid in the increased transfer of drugs to cancerous sites [ 159 ].

3.6.4. Targeting Drug-Resistant Tumors

Metastatic colon tumor cells that overexpress integrin α5β1 have been found to be targeted by PEGylated liposomes altered with a fibronectin-mimetic peptide [ 160 ]. NPs have been made to increase endocytosis when targeting multidrug-resistant tumors, or to bypass or inhibit efflux pumps on the membrane, considering various methods of drug resistance in cancer cells [ 161 ]. As an effective inhibitor of P-gp, TPGS 1000 ( d -alpha-tocopheryl polyethylene glycol 1000 succinate) has become one of the dominant surfactants that increases the cytotoxicity of the G-185 cells of colchicines, doxorubicin, paclitaxel, and vinblastine, which can be compared to that of parental cells [ 162 ]. Another promising and important example of a modifying substance for P-gb is the pluronic block copolymer (P85). In P85 treatment, membrane fluidization gives rise to an interference with metabolic mechanisms and the inhibition of the P-gb ATPase drug efflux system [ 163 ]. The NP system is made up of a lipid shell and a polylactic-co-glycolic acid (PLGA) doxorubicin-conjugated polymer core composed of cholesterol, PEG distearoylphos-phatidylethanolamine, and phosphatidylcholine. To cause vascular disruption in cancer cells, these NPs are filled with a natural phenolic compound called combretastatin [ 164 ].

To be overexpressed on the surface of drug-resistant cancer cells, NPs with folate acid ligands that can attach to folate receptors were shown to obtain particular accumulations in cancerous cells. The NP transport system for the comprehensive and synergistic roles of cancer nano-chemotherapy may be improved by means of attempts to co-govern drugs with ultrasound and photodynamic therapy and thermosensitive therapy [ 165 , 166 ].

3.6.5. Personalized Therapy for Cancer

ανβ3-targeted para-magnetic NPs have been used to study angiogenesis in great detail, as well as to study nascent melanoma cancers non-intrusively, [ 167 ]. The efficacy of treatment, specifically in case of melanomas, can potentially arise through early detection [ 168 ]. To target malignant tumors with greater specificity and affinity, NPs associated with bio-targeting ligands, for example, small molecules, peptides and monoclonal antibodies, can be employed. In regard to each person’s molecular profile, these advancements offer opportunities for the development of tailored oncology, in which tumor therapy, diagnosis and detection are personalized [ 169 ].

Targeted towards tumors, tissue, cells, or organs, and governed by an external magnetic field, iron oxide NPs can be used to attach themselves with nucleotides, proteins, antibodies, and drugs. Towards cellular receptors such as urokinase plasminogen activator receptor, magnetic iron oxide NPs are currently being used. With the aim of improving the effectiveness of drug transport conducted by receptor-mediated endocytosis and for the destruction of cancer stromal fibroblasts, this nano-construct allows the immersion of drug-delivering NPs in the endothelial cell layer of the tumor, tissues, or cancerous cells. Due to their spatial imaging ability and increased biocompatibility, these iron oxide NPs may find significant applications in cancer treatment and imaging [ 170 ]. Breast cancer cells expressing HER2 receptors can be attached by means of the HER2 antibody (herceptin) trastuzumab, conjugated with iron oxide NPs. When attached to the tumor magnetically, it can exhibit increased antitumor activity with cytotoxic molecules such as doxorubicin [ 171 ].

3.6.6. Cancer Treatment through Thermal Ablation

Metallic NPs have shown a capacity for implementation in targeted hyperthermic therapy, particularly in the case of carbon nanotubes, gold silica nanoshells, iron oxide nanoparticles, and solid gold NPs [ 172 , 173 ]. To treat deep tissue cancers, iron oxide NPs have been employed as both therapeutic and diagnostic nanoscale agents [ 174 ]. An increased amount of gold NPs could be obtained by marking gold NPs with antibodies in opposition to specific tumor cells. The application of radio-frequency fields to cells caused the confined heat and death of tumor cells, after the incorporation of NPs [ 172 ]. Through the utilization of magnetically induced heat, magnetic NPs provide an encouraging method for the minimally intrusive excision of small cancers in the breast [ 137 , 175 ]. This approach has the value of allowing the refined and selective tuning of the degree of energy deposition, permitting sufficient temperature control at the target site, and this method also meets the enhanced need for breast-conserving therapies [ 176 ]. The anti-human epidermal growth factor receptor 2 antibody can be employed in transporting drugs to human epidermal growth factor receptor 2-overexpressing tumors, and can initiate an anticancer response [ 175 ]. A pegylated colloidal GNP (gold nanoparticle) consisting of tumor necrosis factor-α attached to its surface called CYT-6091 has been shown to increase thermal therapies and has been broadly investigated as an adjuvant [ 177 ].

Furthermore, to treat tumors via the induction of hyperthermia, superparamagnetic NPs show attractive properties [ 178 ]. There is a transformation of magnetic energy into thermal energy when these NPs are subjected to an alternating magnetic field of adequate frequency and strength. The heat produced is then transported to the cells revolving around the NPs. Once the protein denatures and the restricted temperature increases more than 40 °C, this can cause tumor cell death via apoptosis [ 179 , 180 ].

3.7. Nanotechnology in the Treatment of Genetic Disorders

3.7.1. alzheimer’s disease.

Alzheimer’s disease (AD), the most prevalent form of dementia, is a neurodegenerative disorder [ 181 , 182 ], the initial symptoms of which include impaired memory and declining cognitive abilities, which lead to damage to the motor system [ 183 ]. A lot of literature supports the positive relationship between the concentration of the soluble aggregates of Aβ peptide and the degree of dementia in AD patients [ 184 , 185 , 186 , 187 ]. They accumulate to form insoluble fibrils, which further aggregate to form characteristic plaques [ 188 , 189 ]. Hence, most of the current research is centered towards the prevention of their aggregation. For this purpose, nanomaterials are exploited, owing to their exceptionally small size and fit for crossing the BBB.

Grape resveratrol (a neuroprotective, anti-inflammatory compound [ 190 ]) and OX26 mAB-conjugated solid lipid nanoparticles (SLNs) can inhibit Aβ aggregation [ 189 ]. SLNs have a hydrophobic lipid core, which allows the dispersion of the drug, thereby increasing its bioavailability [ 191 , 192 ]. Moreover, they are rapidly opsonized and clarified from the blood stream, which presents a convincing argument that these SLN do not accumulate in the blood stream unnecessarily, hence cutting down on the associated threats [ 193 ]. Similarly, the monoclonal antibody against fibrillary human amyloid β42 was conjugated with iron oxide NPs that successfully targeted aggregates in the arterioles of mice [ 194 ].

Curcumin and water-soluble PLGA-NPs conjugated with Tet-1 peptide can also destroy amyloid conjugates [ 195 ]. Curcumin, which has anti-mutagenic, anti-inflammatory, antioxidant, anti-cholesterol, anti-tau hyperphosphorylation, and anti-amyloid properties, is an excellent candidate for AD treatment [ 196 , 197 , 198 , 199 , 200 , 201 , 202 ]. B6 peptide was conjugated with curcumin-loaded PLGA-NPs [ 203 ], which decreased the diameter of curcumin, enhancing its cellular uptake. Additionally, they prevented tau hyperphosphorylation and deposition and boosted learning and memory in mice. Memantine, a neuronal death-preventing drug [ 204 ], has also been loaded into PEG-coated PLGA-NPs, which reduced β amyloid plaques and the characteristic inflammation of AD [ 205 ]. Negatively-charged gold nanoparticles (AuNPs) have also been proven to be effective against amyloids, since in their bare form they inhibited Aβ fibrillization and dissociated fibrils [ 206 ]. This finding marks them as potential carriers for anti-AD drugs. Protein capped cadium sulphate (PC-CdS) and iron oxide NPs exhibit anti-tau aggregation properties, while keeping the viability of neuroblastoma cells intact. Moreover, PC-CdS NPs can also disaggregate Tau cells [ 194 , 207 ].

3.7.2. Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease [ 208 ]. Dopaminergic (DA) neurons in the substantia nigra pars compacta selectively die and α-syn Lewy bodies start forming [ 209 , 210 ]. Six mutations are found to be behind familial PD—SNCA, DJ-1, parkin, PINK 1, ATP13A2, and LRKK2 [ 211 ]. Since α-syn’s connection to PD emergence has been established, scientists are now searching for new methods to interfere with its expression [ 212 ]. In a recent study, an N -isopropylacrylamide derivative was immobilized on oleic acid along with short hairpin RNA (shRNA) and loaded in magnetic iron oxide NPs. Nerve growth factor was also added to N -isopropylacrylamide. ShRNA interfered with α-syn synthesis successfully, thereby making it a potential tool for treating PD.

Retinoic acid (a neuroprotective chemical) NPs have also been used and found to be therapeutic for DA neurons. They also induced the production of mRNA and transcription factor proteins that make the survival of DA neurons possible, namely, Nurr 1 and PitX. This makes them suitable for use in the prevention of PD onset [ 213 ]. The co-loading of curcumin and piperine, which have extraordinary cognitive and antioxidant properties, on glycerly monoleate NPs has been performed recently. These NPs were coated with several surfactants that increased the bioavailability of loaded compounds. According to in vivo results, they can inhibit α-syn and reduce oxidative stress, apoptosis, toxicity induced by rotenone, and restrain DA’s neuronal degeneration process [ 214 ].

RNA interference (RNAi) can knockdown specific genes. In a study, α-syn-targeting RNAi and polyethylenimine NPs were used to treat incurable neurodegenerative disorders such as PD [ 215 ]. In a matter of 5 days, the α-syn level was reduced by almost 50% and no side effects (such as the induction of toxicity) were observed. PEG has also been exploited for use in the treatment of PD. PLGA-loaded NPs were coated with lactoferrin, which enhanced the delivery of loaded rotigotine. The results indicated that the cells that came in contact with it did not compromise their viability. In fact, free rotigotine was toxic. It was also reported that a high amount of rotigotine was heterogeneously distributed to the striatum, which is a primary affected region in PD [ 216 ].

3.7.3. Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is another neurodegenerative disorder which is characterized by affected upper and lower motor neurons, the spinal cord, and the motor cortex region. Abnormal amounts of mutant superoxide dismutase (SOD) are also observed in ALS patients. The orderly progression of the disease has been explained by misfolded SOD 1. Hence, research is largely channeled towards reducing the levels of SOD [ 217 ]. Antisense oligonucleotides (ASOs) can effectively silence the proteins but their inability to cross the BBB rendered them useless. However, to overcome this problem, ASOs were loaded onto calcium phosphate lipid-coated NPs. When these were negatively charged, they successfully delivered ASO into a neuron-like cell line [ 218 ].

Oxidative stress and damage have also been reported to contribute to ALS. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) damage DNA, RNA, and other molecules [ 219 ]. Cerium NPs can take part in coupled redox reactions that neutralize ROS and RNS. This makes them suitable for use in antioxidant therapy for a number of neurodegenerative disorders, including ALS [ 220 ].

3.7.4. Huntington’s Disease

Huntington’s disease (HD), an autosomal-dominant neurodegenerative disorder, is characterized by anxiety, involuntary movements, and chorea [ 221 , 222 ]. It has been observed that biological materials obtained from patients with neurodegenerative diseases such as Huntington’s exhibit oxidative stress and mitochondrial defects. HD brains have faulty electron transport chains as well [ 223 ]. 3-nitroproponoic acid (3-NP) is a neurotoxin which leads to the generation of ROS; therefore, researchers are looking for new agents that can potentially inhibit the production of 3-NP.

Curcumin has also been used to treat Huntington’s disease, along with SLN. They can ameliorate 3-NP induced in HD mice by decreasing the amount of intermediate complex II activity. The signs observed include reduced swelling of the mitochondria, lipid peroxidation, and ROS production. Neuromotor coordination was also enhanced [ 224 ]. SLNs have been loaded with rosmarinic acid and introduced into 3-NO-induced mice and this also showed promising results [ 225 ]. β cyclodextrin (CD) NPs have also been used to carry siRNA, which can silence or modify the expression of mutant HTT. CDNPs decreased the amount of mutant gene mRNA dramatically and also showed partial toxicity, but the overall toxicity profile was satisfying [ 226 ].

Trehalose-loaded zwitterion NPs inhibit amyloid and polyglutamine aggregation in HD mice brains [ 227 ]. Their zwitterionic shell enhances cell uptake without inducing cytotoxicity. It hindered aggregation by forming multivalent bonds. This method requires trehalose in micro amounts; however, when used in molecular form it is needed in milli-molar concentrations. Trehalose and zwitterion are other anti-amyloidogenic molecules.

3.7.5. Cystic Fibrosis

Cystic fibrosis is a fatal genetic disorder caused by a mutation in the cystic fibrosis transmembrane conductance (CFTR) gene. It is characterized by abnormal transportation in endothelium cells of a number of tissues. This leads to abnormally thick and sticky mucus, which blocks organs. The chief blocked organ is the lung. This translates into the emergence of recurrent bacterial infections, which destroy the lung tissues progressively, and as a result, pulmonary disease grows large enough to cause mortality [ 228 , 229 ]. To treat this disease, correction of the CFTR gene seems like an attractive option.

Chemically altered mRNA was loaded onto lipid NPs. It was reported that this allowed an increase in the number of membrane localized CFTR, restoring its primary function of acting as a chloride channel. Additionally, the nasal application of these NPs restarted chloride transport to nasal airway epithelium cells. This proved to be an effective tool for CFTR treatment that can be manipulated in the future.

PLGA-NPs coated with PEG have been employed for almost every genetic/neurodegenerative disorder, including cystic fibrosis as well. In this case, they effectively delivered anti-inflammatory compounds and CFTR correctors [ 230 ]. Another interesting approach employed for the treatment of CFTR infections was loading biodegradable NPs with antibiotics, such as ciprofloxacin complex. This approach was adopted to fight the infections that are characteristic of the disease itself. The bacteria which were targeted by these antibiotic-loaded NPs were Pseudomonas aeruginosa . Mucus was checked and analyzed for results after treatment. It was reported that colloidal stability was proven and that the mucus became noticeably less turbid, showing a decrease in pathogenic bacteria [ 231 ]. Table 2 summarizes the outcomes of some nanomaterials employed to treat various genetic disorders.

Summary of the various nanosystems used for treating genetic disorders.

3.8. Nanotechnology in the Treatment of Nervous System Diseases

Fortunately, NPs are not only valuable for genetic or neurodegenerative disorders; they have also been manipulated to treat other severe neurological traumas, such as in post-stroke neuroprotection and spinal cord injuries. These two areas might sound very complex, but studies have proven over time that nanotechnology can help to fight these severe diseases. Regeneration or repair in the central nervous system is another large problem. This is a prevalent problem because the damaged axons lack the ability to regenerate and regrow. The obstacles in the way of the regeneration of these axons are extrinsic inhibitory molecules and an age-dependent drop in intrinsic regenerative capacity, along with some other factors [ 232 , 233 ]. Presently, researchers are investing their efforts in looking for alternative ways to inhibit the action of factors that do not promote the growth and regeneration of damaged axons and neural cells. In this regard, nanotechnology is found to be a highly effective potential tool to treat central nervous system disorders [ 234 ].

For the treatment of spinal cord injuries, conventional drugs are used, which have become unpopular due to drawbacks associated with them. These drugs, when systematically administered, were found to be highly inefficient since they were metabolized rapidly before reaching the target and were cleared from the bloodstream. Now, the aim is to modify them in such a way that their bioavailability can be enhanced. For this purpose, adenosine was conjugated with lipid squalene into nano-assemblies. This method showed astonishing results, since the neurologic deficit score was improved and early motor recovery of the hind limbs was also observed [ 235 ].

Macrophages have been observed to perform a key role in the entire inflammation process in microglia and macrophages and they contribute to the chronic phase of neurodegeneration; hence, they have been established as a therapeutic target [ 236 ]. Polymethyl methacrylate NPs have been used to target specific cell populations of macrophages in order to decrease inflammation without exhibiting toxicity [ 237 ]. A charged surface and surface PEGylation enhance this process, allowing cellular uptake. This is a different approach for the treatment of such diseases. Table 3 summarizes the outcomes of some nanomaterials employed with and without drugs in an effort to treat some major neurodegenerative disorders.

Summary of the various nanosystems used for the treatment of central nervous system disorders.

4. Conclusions and Future Perspectives

Nanotechnology research has grown exponentially within the last few decades, and the focus on healthcare sectors has increased in parallel. Theranostic development has led to a significant amount of understanding of some of the complex etiologies involved, as well as increasing the chances of early diagnosis and therapeutic potential with the help of nanomedicine. Various nanosystems have been exploited and integrated at a limited scale but have proven to be efficient in solving various bottlenecks in various healthcare sectors. However, nanomedicines and nanodevices are still at an early developmental stage and one way to accelerate this process is to direct research studies so that researchers work towards developing new methods to overcome the associated limitations. The gradual development of nanotechnology-based methods has given rise to a hope that soon life-threatening and disabling disorders will be effectively treated. The gaps due to inadequate efficacy and preclinical safety studies need to be filled on a priority basis so that we can make full and timely use of the great potential of nenotechnology, which is yet to be realized. Nanotechnology has a solution to many problems, but this does not mean in any way that there are no challenges or limitations associated with it.

One of the major obstacles in the implementation of nano-based products in living systems for healthcare services is toxicity. Various nanomaterials have triggered unwanted allergic and other reactions that can be potentially harmful to the body. Toxicity is a very complex concept in itself because it is dependent on a diverse range of factors such as morphology, size, dose, surface area, route, and duration of administration [ 246 ]. This directs our attention towards another area, which is the need to standardize or personalize the use of nanomaterials. Furthermore, the reliability and reproducibility of experiments involving NPs remains another area that needs to be worked on. Since these are extremely small entities, controlling their activity in sensitive environments is also hard. Some other limitations are their high cost, the presence of impurities, their environmental impacts, etc. [ 247 ]. If these dangers are not dealt with carefully, they may have seriously lethal repercussions.

Since nanotechnology is a relatively new area, it remains relatively underexplored. In fact, we cannot say that the physiochemical behavior of these NPs is fully known in vivo and in vitro. This is why we might not judge accurately that which type of nanomaterial will be used precisely for what purpose. There are some NPs that might be very useful in one system, but in other systems they might be entirely toxic. One example of such a case is PEI, which is an excellent transporter of nucleic acids, but it shows cytotoxic traits [ 237 ]. Another factor that we tend to ignore is that the NPs have varying compositions, sizes, and shapes and each of them has different impacts on living systems. Moreover, the duration exposure, as well as the coating, aggregation, charge and solubility of nanomaterials, also influence their performance [ 237 ].

Despite the sophisticated instruments and tools developed in recent times, we still need to develop modern tools that can quickly characterize synthetic nanomaterials, separately from existing analytical tools. We are also in dire need of establishing standardized protocols to synthesize these nanomaterials, not only ensuring high yields, stability, and purity, but also complying with the issued security guidelines. An efficient in vivo monitoring system can considerably boost biomedical processes such as the treatment and diagnosis of various serious diseases [ 248 ]. There is also a need to come up with mechanisms that help us to thoroughly understand the fate of NPs once they have been used. These questions include how long they stay in the body, what conditions impact the duration of degradation, how to make them stay for longer and shorter periods, what are their long-term and short-term impacts, how exactly does the body behave towards these outsider entities on a micro and a macro level, what are their characteristics and their mechanisms of action, and how we can standardize these particles to ensure the reproducibility of experiments. These should be addressed before the implementation of nanotechnologies in healthcare sectors. Apart from these, there are also many questions that require well-studied and well-experimented answers. We also need to identify the potential hazards associated with these nanomaterials in order to avoid any unforeseen circumstances. Furthermore, the different nanomedicines and nanoformulations targeting various diseases must be meticulously designed in order to achieve the safest and most efficacious therapeutic regimen. We conclude with the vision that nanotechnology will push forward to develop more promising therapies to cope with various severe diseases, and will also provide researchers with effective tools to solve the various bottlenecks in healthcare sectors.

Author Contributions

Conceptualization, S.A. and C.H.; methodology, W.F.; software, H.F.; validation, S.I., S.A. and B.H.A.; formal analysis, I.A.; investigation, W.F.; resources, C.H.; data curation, S.A.; writing—original draft preparation, S.A., W.F., S.I. and H.F.; writing—review and editing, S.A.; visualization, B.H.A.; supervision, S.A.; project administration, S.A. and I.A.; funding acquisition, C.H. and B.H.A. All authors have read and agreed to the published version of the manuscript.

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Data availability statement, conflicts of interest.

The authors declare no conflict of interest.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.


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Research: What Companies Don’t Know About How Workers Use AI

  • Jeremie Brecheisen

research article in nanotechnology

Three Gallup studies shed light on when and why AI is being used at work — and how employees and customers really feel about it.

Leaders who are exploring how AI might fit into their business operations must not only navigate a vast and ever-changing landscape of tools, but they must also facilitate a significant cultural shift within their organizations. But research shows that leaders do not fully understand their employees’ use of, and readiness for, AI. In addition, a significant number of Americans do not trust business’ use of AI. This article offers three recommendations for leaders to find the right balance of control and trust around AI, including measuring how their employees currently use AI, cultivating trust by empowering managers, and adopting a purpose-led AI strategy that is driven by the company’s purpose instead of a rules-heavy strategy that is driven by fear.

If you’re a leader who wants to shift your workforce toward using AI, you need to do more than manage the implementation of new technologies. You need to initiate a profound cultural shift. At the heart of this cultural shift is trust. Whether the use case for AI is brief and experimental or sweeping and significant, a level of trust must exist between leaders and employees for the initiative to have any hope of success.

  • Jeremie Brecheisen is a partner and managing director of The Gallup CHRO Roundtable.

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  24. Research articles

    A light-fuelled nanoratchet shifts a coupled chemical equilibrium. An artificial molecular machine was designed by coupling a chemical equilibrium to a photoresponsive molecular motor. Upon light ...


    Through a comprehensive analysis of recent research and development efforts, this abstract underscores the critical role of nanotechnology in accelerating the transition to a sustainable and ...

  26. Four from MIT named 2024 Knight-Hennessy Scholars

    Outside of research, Colicci served as co-director of TEDxMIT and propulsion lead for the MIT Rocket Team. He is also passionate about STEM engagement and outreach, having taught educational workshops in Zambia and India. Owen Dugan. Owen Dugan, from Sleepy Hollow, New York, is a senior majoring in physics. As a Knight-Hennessy Scholar, he will ...

  27. U.S. Tightens Rules on Risky Virus Research

    Research on extinct pathogens will draw the highest levels of scrutiny. Dr. Evans also noted that the new rules emphasize the risk that lab research can have on plants and animals.

  28. Emerging Applications of Nanotechnology in Healthcare Systems: Grand

    1. Introduction. Nanobiotechnology, a recently coined term, emerged from the blending of molecular biology and nanotechnology. It is a branch of science which revolves around structures or functional materials at the nanoscale, which are produced by employing both physical and chemical methods [].In the last thirty years, the discipline of nanotechnology has been a crucial area of research ...

  29. Research: What Companies Don't Know About How Workers Use AI

    This article offers three recommendations for leaders to find the right balance of control and trust around AI, including measuring how their employees currently use AI, cultivating trust by ...

  30. Articles in 2021

    Quantum nanoscience. Nanoscale systems are ideally suited to study quantum mechanical effects and explore these as resources for emerging quantum technology such as quantum sensing, communication ...