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Review

Recent Advances in Nanoparticle-Mediated Co-Delivery System: A Promising Strategy in Medical and Agricultural Field

by
Mingshan Li
1,
Xiaowei Sun
1,
Meizhen Yin
2,
Jie Shen
1,* and
Shuo Yan
1,*
1
Department of Plant Biosecurity and MARA Key Laboratory of Surveillance and Management for Plant Quarantine Pests, College of Plant Protection, China Agricultural University, Beijing 100193, China
2
State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(6), 5121; https://doi.org/10.3390/ijms24065121
Submission received: 21 February 2023 / Revised: 5 March 2023 / Accepted: 6 March 2023 / Published: 7 March 2023
(This article belongs to the Special Issue Molecular Nano-Architectures 2.0: Chemistry and Physics)
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Abstract

:
Drug and gene delivery systems mediated by nanoparticles have been widely studied for life science in the past decade. The application of nano-delivery systems can dramatically improve the stability and delivery efficiency of carried ingredients, overcoming the defects of administration routes in cancer therapy, and possibly maintaining the sustainability of agricultural systems. However, delivery of a drug or gene alone sometimes cannot achieve a satisfactory effect. The nanoparticle-mediated co-delivery system can load multiple drugs and genes simultaneously, and improve the effectiveness of each component, thus amplifying efficacy and exhibiting synergistic effects in cancer therapy and pest management. The co-delivery system has been widely reported in the medical field, and studies on its application in the agricultural field have recently begun to emerge. In this progress report, we summarize recent progress in the preparation and application of drug and gene co-delivery systems and discuss the remaining challenges and future perspectives in the design and fabrication.

1. Introduction

Over the past decade, nanotechnology has been at the forefront of rapid advances in fields as diverse as medicine, electronics, aerospace, life science, and agriculture [1,2]. The application of nanomaterials can break through the bottleneck of many traditional crafts and provide strong technical supports for nano-delivery platform, thus becoming a research hotspot in the fields of medicine and modern agriculture [3,4,5]. Since the first research on the delivery of drugs by nanomaterials, there have been numerous reports of the application of nanomaterials to deliver active ingredients (AIs) [6,7,8]. To date, many nanomaterials are employed for a nano-delivery system due to their unique physicochemical properties, such as controllable size, low cytotoxicity, enhanced activity of carried ingredients, and breaking the biofilm barrier. For example, polymeric NPs are fabricated from natural and synthetic polymers and are characterized by low cost and biodegradability [9]. Lipids are amphiphilic molecules consisting of a polar head group, a hydrophobic tail, and an intermediate linker [10]. Inorganic NPs are usually synthesized by chemical methods using heavy metal or inorganic material, such as mesoporous silica NPs [11,12], iron oxide NPs [13], gold NPs [14], and quantum dots, etc. [15]. Recently, plants or crops have also been used as feed stocks to develop green synthetic methods [16,17]. Multiple nanoparticles (NPs) have been designed and evaluated as carriers to deliver small molecule drugs for medical or agriculture field, including polymeric NPs, lipid NPs and other inorganic NPs [18,19]. In addition, NPs can deliver various nucleic acid molecules, proteins or photosensitizers, which have been extensively investigated [20,21,22].
Chemotherapy, biological therapy, and radiation therapy are the main forms of cancer treatment, and the former is also considered to be one of the most effective methods in clinical practice [23]. In chemotherapy, patients are often treated with cytotoxic drugs to kill cancer cells [24]. Biological therapy involves the application of biomacromolecules such as nucleic acids to inhibit specific molecules that affect tumor growth [25]. However, the use of chemotherapeutic agents is limited by three major limitations, such as poor water solubility, poor bioavailability, and toxicity of normal tissues [26]. Poor solubility and bioavailability often result in irregular biodistribution and systemic toxicity of chemotherapeutic drugs, which in turn affect normal cells. Multidrug resistance (MDR) caused by long-term and continuous administration is considered as a harmful consequence [27,28,29]. Thus, after extensive attempts, researchers have developed multifunctional vectors that can precisely deliver therapeutic drugs to the site of action. Currently, new therapeutic strategies have been developed to improve treatment efficiency and reduce costs and side effects [30,31,32].
With nano-delivery platforms, small molecule drugs or nucleic acid molecules can be efficiently transported to target tissues without degradation [7,33]. However, single delivery of chemotherapy targeting one pathway is usually not enough, and multiple reasons (such as MDR) hinder the development of effective and long-lasting cancer treatments. Therefore, the combination of different treatments (delivery of genes or drugs) has been proposed as a more ideal cancer treatment strategy and widely studied [34,35,36]. Co-delivery systems can improve the pharmacokinetics and physicochemical properties of therapeutic drugs and improve the efficacy of combination therapy through targeted design of drug delivery regimens [37]. Many combination applications have been designed to achieve synergistic therapeutic effect, and the co-delivery of multiple AIs in the same nanocarrier may achieve desirable effects [38].
Pesticides play a vital role in defending against biological disasters and promoting crop productivity [39]. Traditional pesticides are synthetic organic compounds with high hydrophobicity, which is inconvenient to apply. Meanwhile, traditional processing and formulation requires organic solvents which further poses environmental pollution and biosafety risks [40,41]. Therefore, there is an urgency in scientific use of pesticides and improve the control efficacy of plant diseases and insect pests for green food production. Nanomaterials can be used as substitutes for organic solvents in processing and formulation. Currently, nano-enabled pesticides (nanopesticides) are considered to be less than 1000 nm in size, including insecticides, fungicides, herbicides, and rodenticides, as well as plant immune inducers, plant growth regulators and other AIs that can improve the resistance of plants [42,43]. For precision agriculture, nanopesticides are prepared in different formats of NPs, which show a variety of appealing characteristics, including long-term stability and duration, controlled and stimulation-regulated release rates, increased AI solubility, and improved adhesion to crops, etc. [44,45,46,47]. Recently, a review provided a comprehensive analysis of nanopesticides in controlling agricultural pests compared with their non-nanoscale analogues from 500 journal articles [48]. The overall efficacy of nanopesticides against target organisms is 31% higher, and the toxicity of nanopesticides toward non-target organisms is 43% lower, highlighting that nanopesticides are potentially more efficient, sustainable, and have a lower adverse impact on the environment.
In this review article, we primarily focus on nanoparticle-mediated co-delivery systems. Combining our own work with evidence from the literatures, we highlight the importance of NPs in delivery and co-delivery systems, summarize the latest research and insights in the field of co-delivery, and hope that we will provide some new ideas and stimulate more efforts to promote the widespread use of nano-delivery system in the medical and agricultural field.

2. Co-Delivery System in Medical Field

Various NPs have been examined to design novel co-delivery systems, which can be divided into inorganic-based NPs and organic-based NPs. The former mostly includes mesoporous silica NPs, iron oxide NPs, metallic NPs (copper, gold, or silver), quantum dots, etc. The latter includes polymeric micelles, polymeric NPs, liposomes, dendrimers, etc. Recent advances in the development of NPs suggest that these systems can be designed to protect and deliver AIs with different types and sizes, ranging from chemical small molecules to biological macromolecules, and from hydrophilic to hydrophobic agents [38]. The drugs and/or genes (cargoes) are enabled by NPs for efficient cellular uptake and arrive at the target after the endosomal escape to take effect separately (Figure 1). In addition to many types of drugs, nucleic acid molecules come in many varieties, including messenger RNA (mRNA) which is decoded into peptides or proteins; microRNA (miRNA), short interfering RNA (siRNA), and double-stranded RNA (dsRNA) that can induce gene silencing; and plasmid DNA (pDNA) that gets further expression in the nucleus, etc.

2.1. Co-Delivery of Drugs

Based on the achievements obtained from the delivery of single chemical drug, co-delivery of two different chemical drugs has been developed and clinically applied to treat different types of cancers [49,50,51]. Compared with monotherapy, combination therapy can not only reduce the possibility of tumor resistance to drugs, but also alleviate the side effects of drugs by reducing the dose of drugs. Different NPs are designed for delivery because of the different physical, chemical and biological properties of these therapeutic agents. Current studies have shown that the delivery of two chemical drugs in the same nanocarrier is much more efficient than a system that delivers a single drug [50,52]. Meanwhile, nanocarriers can improve the water solubility and delivery efficiency of hydrophobic drugs in vivo.
On this basis, co-delivery of other chemotherapeutic drugs or natural active products also achieves synergistic therapeutic effect [53]. Chao and co-workers reported a mesoporous magnetite ferrite NP as an inorganic drug carrier, which can efficiently encapsulate hydrophobic drug (rifampin) and simultaneous co-load hydrophilic drug (isoniazide) [54]. Besides, the prepared NPs exhibit excellent biocompatibility and cellular uptake, which can enhance drug loading capacity and solve the delivery problem of hydrophobic drug molecules [55]. Karimifard et al. fabricated chitosan-adorned niosome nanocarriers for co-delivery of doxorubicin (DOX) and vincristine to reduce drug dose and overcome MDR [56]. The complex effectively inhibits cell migration and induces the apoptosis of breast cancer cells. In addition, the complex shows significant drug release in acidic pH compared to physiological pH, decreasing the adverse off-target effects on normal cells. The overexpression of the drug efflux pumping on the cell membrane is one of the main mechanisms causing MDR, that limits the chemotherapy efficacy [57]. For example, P-glycoprotein (P-gp) encoded by the mdr-1 gene is a key protein on cell membranes and a major drug efflux pump that pumps the drug out of tumor cells. Tian et al. co-delivered heparin and quercetin to breast cancer cells, achieving targeted combination chemotherapy and MDR reversal [58]. The complex can significantly block tumor lymphatic formation and inhibit the expression of P-gp in tumor cells.
In addition to co-delivery of two chemotherapy drugs, co-delivery of drugs and other cargos has also been studied. For example, Hu et al. developed the co-delivery system of the hydrophobic chemotherapeutic drug paclitaxel and biomacromolecule interleukin-12 (IL-12) based on the mPEG-Dlinkm-PDLLA [59]. The NPs are enriched in the tumor site, which can significantly inhibit the growth and metastasis of breast cancer cells 4T1 and prolong the overall survival of tumor-bearing mice.

2.2. Co-Delivery of Genes

Nucleic acid-based gene therapy is based on therapeutic molecules DNA or RNA, which aims to achieve multiple goals in vivo, including (1) deliver siRNA, miRNA or dsRNA for gene down regulations; (2) deliver pDNA or mRNA for gene over expression [60,61]. Co-delivery of the nucleic acids has the potential to regulate target gene expression level, hence changing protein content and even disease development. Similar to co-delivery of antitumor drugs, different formulations containing various nucleic acid molecules have been screened for overcoming MDR [62]. Some researchers have explored the co-delivery of dual-gene nanoplatforms, such as siRNA-siRNA, pDNA-siRNA, siRNA-miRNA, etc., to treat various diseases related to genetic disorders or cancers [59,60,61].
In 2013, Tabernero et al. used lipid NPs to co-deliver two modified siRNAs and performed the first human clinical trials [63]. Ball et al. established the co-delivery system of siRNA and mRNA based on the same lipid NP that can enhance the efficacy of both agents in vitro and in vivo [64]. NPs co-delivering siRNA and mRNA can mediate significantly higher levels of gene silencing compared to NPs loading siRNA alone. When the same set of cells is assessed for mRNA delivery, the co-delivery system again produces better results. Yang et al. used nano-carriers to co-deliver K-ras and Notch siRNA [65]. This strategy increases the sensitivity of pancreatic cancer cells to the chemotherapy drug gemcitabine and also helps to resolve MDR. Wang et al. designed and constructed liposomal NPs loaded with both p38α MAPK and p65 siRNA [66]. The complex efficiently silences two genes, and eventually alleviates the proteinuria and inflammation in mouse IgAN models. This suggests that co-delivery of nucleic acids plays a role not only in cancer treatment, but also in other disease treatment. With the development and optimization of gene therapy, the CRISPR/Cas system has been studied and developed over years, and it has the potential to enable true cure therapies that fight disease at the DNA level and address its origin rather than just treating its symptoms [67]. The non-viral delivery (nanoparticle delivery system) has been studied and widely used in gene editing, and NPs can effectively deliver CRISPR/Cas9 systems into targeted cells [68,69]. For cancer therapy, Cas9 protein/mRNA/pDNA and single guide RNA (sgRNA) co-delivery system have been designed to knock out tumor-related genes and suppress tumor growth. As an example, Wang et al. developed PEGylated NPs co-delivering Cas9 expression plasmids and sgRNAs, and the gene editing efficiency can reach 35%, which results in significant tumor suppression (higher than 71%) and improves the survival rate of tumor-bearing mice (60%) [70].

2.3. Co-Delivery of Genes and Drugs

Although many effective research studies and treatments have been made, nucleic acids face the same problems with cancer heterogeneity and adaptive resistance as traditional small molecule drugs in cancer therapy. With the achievements obtained from the fields of chemotherapy and gene therapy, co-delivery of drugs and genes has attracted wide attention in combination therapy due to its synergistic therapeutic effects [71,72,73]. The general incentive behind the co-delivery system is to disrupt MDR signaling pathways. For example, the combination of anticancer drugs and siRNA has great potential in cancer treatment to achieve synergistic effect and overcomes the hurdlers of using a single drug [74,75]. Zhang et al. reported the graft copolymer-based co-delivery of DOX and siRNA targeted P-gp, that exhibited good effects on reversing MDR and synergistic cancer therapy [76]. This co-delivery can down regulate the expression of P-gp, enhance the cytotoxicity of DOX, and suppress the growth of tumor more effectively than free DOX or DOX/NPs complex in tumor-bearing mice. Similarly, Joshi and co-workers fabricated the hypoxia-sensitive micellar NPs for co-delivery of DOX and siRNA targeted P-gp. Under hypoxic conditions, this combination was 80% cytotoxic in monolayer cells and 20% cytotoxic in spherical cells [77]. Meanwhile, researchers used the gold NPs for delivering both DOX and morpholino AONs, which is one of the modified gene silencing DNA analogs [14]. This complex provides enhanced intracellular uptake of DOX, and co-delivery of morpholino and DOX shows better treatment efficiency compared to the free drug.
In addition to the treatment regimen of reversing MDR, induction of tumor apoptosis through co-delivery of chemotherapy drugs and therapeutic genes is another possible cancer treatment strategy. Recently, a co-delivery system was designed to simultaneously deliver curcumin and p53 DNA to enhance the sensitivity of drug-resistant ovarian cancer cells to cisplatin [78]. In a different example, a polycationic brush was used as a nanocarrier for co-delivery DOX and pDNA of p53 [79]. The obtained DOX-NPs/pDNA complexes can transport DOX and pDNA into the same cell. The synergistic delivery of DOX and p53 genes enhances the cell growth inhibition and reduces the dose of DOX.

3. Co-Delivery System in Agricultural Field

In agricultural and environmental fields, some nanoparticles can be used alone due to their own properties [80]. Metal oxides TiO2 have been shown to have excellent dye degradation activity and can be applied for environmental remediation [16,81]. Biosynthesized AuNPs modulated the accumulation of nitric oxide and induced salt stress tolerance in wheat plants [82]. Meanwhile, NPs can be directly used as nanopesticides due to their antibacterial or insecticidal properties [81]. For example, copper oxide and calcium oxide NPs can be used to control Spodoptera littoralis [83]. Bharani et al. synthesized nanosilver with a good control effect against Spodoptera litura [84]. NPs exhibit not only biotoxic properties but also plant disease resistance. The use of silver NPs can control tomato early blight and increase the fresh weight of tomato by 32.58% [85]. Furthermore, NPs can load AIs by means of adsorption, entrapment, and encapsulation to prepare nanocapsule, nanosphere, nanomicelle, and other formulations [86].

3.1. Nanoparticles Deliver Pesticides (Drugs)

Nanopesticides are similar to other common pesticide formulations in that they help to improve the apparent solubility of the insoluble AIs, or release the AIs in a slow or targeted manner, thereby protecting them from premature degradation [87,88,89]. For nanopesticides composition, AIs can be loaded on the inorganic NPs surface, incorporated into the pores of porous NPs or conjugated with polymer. The high surface-to-volume ratio of silica NPs has been widely used as nanofertilizers and nanopesticides [90,91]. In a foliar nitrogen fertilizer study, sea urchin-like micro- nanostructured hollow silica spheres with 500 nm particle diameter were used to load a nitrogen fertilizer to improve the utilization rate on plant leaves [92]. Compared with traditional fertilizer, the utilization rate of nanofertilizer increased by 2.29 times, and the adhesion ability of nanofertilizer on peanut and corn leaves increased by 5.9 times and 2.2 times, respectively. Zhu et al. synthesized mesoporous silica NPs to deliver fenoxanil into rice plants, suggesting that the distribution behavior of pesticides in plants can be regulated by NPs [93].
Polymeric NPs are of significant interest for encapsulation of pesticides due to many unique features such as renewable, biodegradable, low cost, and environmental responsibility [94]. Yan et al. used a polymeric NP (Star polycation, SPc) to assemble with botanical pesticide matrine, reducing its particle size to 10 nm in aqueous solution and amplifying its bioactivity by about 20% in vitro and in vivo [95]. The SPc can not only increase the bioactivity of loaded pesticides, but also reduce pesticide residue [89,96]. The SPc can also assemble with calcium glycinate to prepare a calcium nutrition nanoagent with nanoscale size (17.72 nm), thus enhancing transport and antiviral immunity [97]. The calcium transport is accelerated into tomato leaves and the protective effect of calcium glycinate is remarkably improved toward tomato mosaic virus. Furthermore, the SPc can activate the endocytosis pathway of plants to amplify the defense responses induced by chitosan elicitor, and NP-loaded chitosan exhibit enhanced control effects against potato late blight [98].
NPs can greatly improve the environmental stability of AIs and build a controlled release system of agents that respond to external pH, enzyme, light, temperature, and other factors [99]. The stimulus-responsive nanocarriers typically employ widely available and biodegradable natural polymers including ethyl cellulose and starch. Liu et al. developed a composite that chemically functionalized chitosan and attapulgite clay as pesticide carriers capable of responding to UV-accelerated release [100]. The release of the pesticide under UV light stimulation is 3.5 times that under natural light, demonstrating a good performance of light-controlled release of the smartly engineered pesticide. Ren et al. used interface polymerization to combine modified biochar and polyurea microcapsules to co-encapsulate allyl isothiocyanate, developing a model fumigant for controlled release [101]. It shows potent bioactivity against soil-borne pathogens and weeds, and further minimizes fumigant usage. The controlled release systems reduce the dosage and frequency of pesticide application, thus improving the utilization rate of pesticides.

3.2. Nanoparticles Deliver Nucleic Pesticides (Genes)

RNA interference (RNAi) is a conserved regulatory mechanism mediated by the siRNA pathway, microRNA pathway, and Piwi-interacting RNA pathway, which can silence or inhibit the expression of target genes [102,103,104]. For nanopesticides, the addition of NPs enhances the stability of nucleic acid molecules and makes them free from degradation. The lipid formulation of dsRNA is protected from the degradation by endonucleases present in Sf9 cell conditioned medium, hemolymph, and mid-intestinal cavity contents of Spodoptera frugiperda [105]. For another example, SPc and perylenediimide-cored cationic dendrimer can prevent dsRNA from degradation by RNase A and hemolymph of aphids and fall armyworms [106].
In addition to shielding and protecting dsRNA from nuclease degradation in the environment, NPs can also facilitate the transport of dsRNA across the membrane and avoid its degradation in endosomes or lysosomes. For instance, a cationic core–shell fluorescent nanoparticle is able to accelerate endocytosis and deliver DNA across cell membrane for efficient cellular uptake [107]. Lu and co-workers designed the block copolymer poly to form well-defined, core–shell NPs to facilitate its passage through various physiological obstacles and thus prolong the survival time of dsRNA in the digestive tract, so as to enter the midgut cells of Locusta migratoria [108]. The SPc can also efficiently deliver dsRNA across the cell membrane and achieve efficient gene silencing [109]. Compared to naked dsRNA, crucial genes regulating endocytosis and exocytosis are remarkably up-regulated in Sf9 cells treated with a dsRNA/SPc complex [106].
RNAi-based strategy has great potential in combatting plant diseases and pests [110,111,112]. Crops can be directly sprayed with dsRNA (spray-induced gene silencing, SIGS) targeting key genes of plant pathogens or pests to induce specific silencing, thus leading to the decline of pest infestation and finally realizing the sustainable eco-friendly pest management [113,114]. A new formulation was developed with the help of a fluorescent NP. The RNA pesticide rapidly penetrates the insect body wall and effectively inhibits gene expression [115]. Meanwhile, Yan et al. applied the dsRNA/SPc formulation targeting V-ATPaseD and chitin synthase1 genes, and direct spray to soybean seedlings infected with Aphis glycines results in a good control effect [116]. The combination of NPs and nucleic acid pesticides can improve RNAi efficiency, deformity and mortality, and become a more sustainable pest management strategy (Table 1). With the reduction of dsRNA synthesis cost, Ma et al. further applied the spray method in the field trail, and the control efficacy was as good as expectated [117]. In addition, NPs can also promote the delivery of dsRNA through root tips in Arabidopsis [118], which is conducive to irrigation and trunk injection development. At present, there are few studies on improving the RNAi efficiency of phytopathogenic fungi by NPs. Additionally, the types of NPs delivering RNA pesticides for plant disease management are relatively single. Wang et al. used a variety of NPs to deliver RNA fungicide, and the delivery efficiency and protective effect of SPc were the best among them [5]. Table 2 presents selected applications of NPs-mediated RNAi in fungi and viruses.

3.3. Application of Co-Delivery System

For synergetic strategy, the co-delivery of multiple pesticides in a single nanocarrier would allow the effective management with low drug concentration, which can help to greatly reduce pesticide residues and environmental contamination. Although pesticide co-delivery systems are rarely reported for agricultural application, efficient and safe co-delivery nanocarriers are necessary for the development of new environmentally friendly pesticides. Suraphan and co-workers utilized premix membrane emulsion combined with S/O/W double emulsion method to further prepare novel AV/CAP co-delivery microcapsule formulations [133]. The administration encapsulated insoluble chlorantraniliprole (CAP) inside the microcapsules and soluble avermectin (AV) into polylactide shells. The particle size of the porous AV/CAP PLA microcapsule is 3.4 µm, and the loading contents of AV and CAP are not obviously different between the co-delivery microcapsules and their corresponding single delivery microcapsules. The co-delivery system shows the lowest LC50 value of 18.1 µg mL−1 compared to the commercial CAP and AV. This is the first attempt of co-delivery in agriculture, but it does not fall under the category of nanopesticides.
Firstly, our team constructed SPc as a low-cost multifunctional nanocarrier that can co-deliver the dsRNA and pesticide to develop a novel multicomponent nano-pesticide against devastating green peach aphids [134]. The SPc can self-assemble with botanical pesticide matrine, and then complex with dsRNA to form a nano-sized matrine/SPc/dsRNA complex, which can be efficiently delivered into Drosophila S2 cells. The dsRNA (dshem) targeting immune gene hemocytin leads to efficient gene silencing and a high mortality rate through SPc-based topical application, and the main lethal mechanism is via the down-regulating hem gene, resulting in severe bacterial infection. In the field trial, the dshem/SPc complex exhibits short persistence, and the matrine/SPc complex shows slow-acting property, exposing their defects. Interestingly, both initial acting time and persistence of co-delivery complex are remarkably improved, which overcomes the disadvantages of both agents. The synergistic effect of co-delivery system based on NPs has achieved good performance in pest control. The co-administration of thiamethoxam and dsRNA of synapsin, both targeting the nervous system, effectively results in the death of melon aphids [135].

4. Limitations and Challenges

While significant advances have been made in co-delivery of drugs and/or genes, a number of issues still need to be resolved before applications. First, the safety and regulatory aspects of nanomaterials are widely concerned. Whether they are used as carriers of medical drugs or pesticides, their own cytotoxicity should be very low. In the application of pesticides, a complete risk assessment is necessary for all aspects of pesticidal nanoformulations, including degradation fate, transport, bioaccumulation, adverse effects, and risk to the environment and human health [48]. In addition, NPs carrying multiple AIs simultaneously will increase in particle size, but relevant studies have confirmed that large size molecules are not easy to cross the cell membrane [136]. In order to achieve the desired drug quality and small particle size requirements, more NPs are required to encapsulate the cargoes, which also raises higher requirements for the safety and design methods of co-delivery systems [137].
As for the fabrication of the co-delivery system, designers need to have a clear understanding of drugs and genes of each component, and fully consider the interactions between nanocarrier and cargo, as well as the synergies between loaded reagents [138,139]. For drug and gene co-delivery systems, the biological distribution and pharmacokinetics of the carried agents will be affected due to the huge differences in physicochemical properties of the two components loaded by NPs, such as the difference in molecular weight and hydrophilicity [140]. For example, Tang et al. constructed a pH-sensitive NP to co-deliver DOX and survivin-targeting shRNA for reversing MDR [141]. The co-delivery system increased the DOX accumulation and down-regulated 57.7% survivin expression. However, in vivo biodistribution studies demonstrated that the copolymer remarkably increased tumor accumulation of DOX by more than 10-fold and shRNA by more than 20-fold. The differences in molecular weight, hydrophobicity, and metabolic stability between small molecule drugs and nucleic acids may greatly affect their biological distribution and pharmacokinetics. The co-delivery of drug-nucleic acid combinations is a challenging task because of the obvious differences in the of the two types of agents. Additionally, the loading method of drug molecules and the synergetic strategy of the co-delivery system need to summarize general rules and explore the optimal design route.

5. Perspectives in Pesticide

The application of NP-based co-delivery systems is mainly divided into synergistic and complementary functions. The co-delivery system, no matter delivering drugs, genes or multiple agents, should be based on solving the bottleneck of pesticide development. Using the synergistic mode of co-delivery system to concentrate on a certain direction, the corresponding drug and nanomaterials can be further reduced and enhanced [135]. For example, the use of co-delivery of conventional pesticides and their corresponding RNA pesticides targeting resistance-related genes avoids the high cost of developing new pesticides and gives traditional pesticides a new lease of life (unpublished data). On the other hand, complementary action in both aspects can reduce the frequency of pesticide application and the dosage of nanomaterials, which is friendlier to the environment [133,134]. For instance, co-delivery of the botanical elicitor cellobiose and dsRNAs of PiHmp1 + PiCut3 targeting Phytophthora infestans achieves dramatic results. The multicomponent nano-pesticide can not only enter into P. infestans more efficiently for gene silencing, but also enhance the systemic resistance of plants. Its protective effect against potato late blight is even higher than that of a widely-used commercial fungicide mancozeb (unpublished data). Although environmental safety of most nanoparticles is still unclear, recent studies have shown that the SPc has some negative effects on non-target organisms at extremely high concentrations [142,143]. To prevent or suppress plant diseases, researchers can develop nanofungicides for plant pathogens; immune inducers and multiple nanofertilizers for plant stress. A variety of insecticides, including chemical or biopesticides and RNA pesticides targeting pests, can be purposefully combined for both above and below ground pests (Figure 2). Multiple application methods including foliar spraying, irrigation, and trunk injection can also be refined to specific applications [113,137]. The production costs of NPs and RNA pesticides should be further reduced, and the application of co-delivery system in the field has been preliminarily realized.

Author Contributions

S.Y. and J.S. conceived the idea and reviewed the literature. M.L., X.S., M.Y., S.Y. and J.S. revised the manuscript. M.L. wrote the manuscript and contributed to the generation of figures. All authors have read and agreed to the published version of the manuscript.

Funding

This work was financially supported by the National Key R&D Program of China (2022YFD1401800).

Conflicts of Interest

The authors declare that they have no known competing financial interest or personal relationships that could have appeared to influence the work reported in this paper.

References

  1. Bayda, S.; Adeel, M.; Tuccinardi, T.; Cordani, M.; Rizzolio, F. The history of nanoscience and nanotechnology: From chemical-physical applications to nanomedicine. Molecules 2020, 25, 112. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  2. An, C.; Sun, C.; Li, N.; Huang, B.; Jiang, J.; Shen, Y.; Wang, C.; Zhao, X.; Cui, B.; Wang, C.; et al. Nanomaterials and nanotechnology for the delivery of agrochemicals: Strategies towards sustainable agriculture. J. Nanobiotechnol. 2022, 20, 11. [Google Scholar] [CrossRef] [PubMed]
  3. Wu, H.; Li, Z. Recent advances in nano-enabled agriculture for improving plant performance. Crop J. 2022, 10, 1–12. [Google Scholar] [CrossRef]
  4. Yan, Y.; Zhu, X.; Yu, Y.; Li, C.; Zhang, Z.; Wang, F. Nanotechnology strategies for plant genetic engineering. Adv. Mater. 2022, 34, 2106945. [Google Scholar] [CrossRef] [PubMed]
  5. Wang, Y.; Yan, Q.; Lan, C.; Tang, T.; Wang, K.; Shen, J.; Niu, D. Nanoparticle carriers enhance RNA stability and uptake efficiency and prolong the protection against Rhizoctonia solani. Phytopathol. Res. 2023, 5, 2. [Google Scholar] [CrossRef]
  6. Roco, M.C.; Williams, R.S.; Alivisatos, P. Nanotechnology Research Directions: IWGN Workshop Report. Vision for Nanotechnology R&D in the Next Decade; Springer: Berlin/Heidelberg, Germany, 2000. [Google Scholar]
  7. Chen, F.; Liu, Q.; Xiong, Y.; Xu, L. Nucleic acid strategies for infectious disease treatments: The nanoparticle-based oral delivery route. Front. Pharmacol. 2022, 13, 984981. [Google Scholar] [CrossRef] [PubMed]
  8. Yang, Z.; McClements, D.J.; Peng, X.; Xu, Z.; Meng, M.; Chen, L.; Jin, Z. Fabrication of zein–carboxymethyl cellulose nanoparticles for co-delivery of quercetin and resveratrol. J. Food Eng. 2023, 341, 111322. [Google Scholar] [CrossRef]
  9. Lai, P.; Daear, W.; Löbenberg, R.; Prenner, E.J. Overview of the preparation of organic polymeric nanoparticles for drug delivery based on gelatine, chitosan, poly(d,l-lactide-co-glycolic acid) and polyalkylcyanoacrylate. Colloids Surf. B 2014, 118, 154–163. [Google Scholar] [CrossRef]
  10. Hou, X.; Zaks, T.; Langer, R.; Dong, Y. Lipid nanoparticles for mRNA delivery. Nat. Rev. Mater. 2021, 6, 1078–1094. [Google Scholar] [CrossRef]
  11. Kamegawa, R.; Naito, M.; Miyata, K. Functionalization of silica nanoparticles for nucleic acid delivery. Nano Res. 2018, 11, 5219–5239. [Google Scholar] [CrossRef]
  12. Kim, M.H.; Na, H.K.; Kim, Y.K.; Ryoo, S.R.; Cho, H.S.; Lee, K.E.; Jeon, H.; Ryoo, R.; Min, D.H. Facile synthesis of monodispersed mesoporous silica nanoparticles with ultralarge pores and their application in gene delivery. ACS Nano 2011, 5, 3568–3576. [Google Scholar] [CrossRef] [PubMed]
  13. Zhang, J.; Zhang, T.; Gao, J. Biocompatible iron oxide nanoparticles for targeted cancer gene therapy: A review. Nanomaterials 2022, 12, 3323. [Google Scholar] [CrossRef] [PubMed]
  14. Tunc, C.U.; Culha, M. Gold nanoparticles conjugated DNA-tile nanomaterials for simultaneous delivery of morpholino antisense oligonucleotides and doxorubicin. J. Drug Deliv. Sci. Technol. 2022, 74, 103546. [Google Scholar] [CrossRef]
  15. Gidwani, B.; Sahu, V.; Shukla, S.S.; Pandey, R.; Joshi, V.; Jain, V.K.; Vyas, A. Quantum dots: Prospectives, toxicity, advances and applications. J. Drug Delivery Sci. Technol. 2021, 61, 102308. [Google Scholar] [CrossRef]
  16. Ahmad, M.M.; Kotb, H.M.; Mushtaq, S.; Waheed-Ur-Rehman, M.; Maghanga, C.M.; Alam, M.W. Green synthesis of Mn + Cu bimetallic nanoparticles using Vinca rosea extract and their antioxidant, antibacterial, and catalytic activities. Crystals 2022, 12, 72. [Google Scholar] [CrossRef]
  17. Pieła, A.; Żymańczyk-Duda, E.; Brzezińska-Rodak, M.; Duda, M.; Grzesiak, J.; Saeid, A.; Klimek-Ochab, M. Biogenic synthesis of silica nanoparticles from corn cobs husks. Dependence of the productivity on the method of raw material processing. Bioorganic Chem. 2020, 99, 103773. [Google Scholar] [CrossRef]
  18. Mogheri, F.; Jokar, E.; Afshin, R.; Akbari, A.A.; Dadashpour, M.; Firouzi-amandi, A.; Serati-Nouri, H.; Zarghami, N. Co-delivery of metformin and silibinin in dual-drug loaded nanoparticles synergistically improves chemotherapy in human non-small cell lung cancer A549 cells. J. Drug Deliv. Sci. Technol. 2021, 66, 102752. [Google Scholar] [CrossRef]
  19. Menon, I.; Zaroudi, M.; Zhang, Y.; Aisenbrey, E.; Hui, L. Fabrication of active targeting lipid nanoparticles: Challenges and perspectives. Mater. Today Adv. 2022, 16, 100299. [Google Scholar] [CrossRef]
  20. Laisney, J.; Rose, V.L.; Watters, K.; Donohue, K.V.; Unrine, J.M. Delivery of short hairpin RNA in the neotropical brown stink bug, Euschistus heros, using a composite nanomaterial. Pestic. Biochem. Physiol. 2021, 177, 104906. [Google Scholar] [CrossRef]
  21. Cheng, Z.; Li, Y.; Zhao, D.; Zhao, W.; Wu, M.; Zhang, W.; Cui, Y.; Zhang, P.; Zhang, Z. Nanocarriers for intracellular co-delivery of proteins and small-molecule drugs for cancer therapy. Front. Bioeng. Biotechnol. 2022, 10, 994655. [Google Scholar] [CrossRef]
  22. Deng, S.; Wang, S.; Xiao, Z.; Cheng, D. Unprotonatable and ROS-sensitive nanocarrier for NIR spatially activated siRNA therapy with synergistic drug effect. Small 2022, 18, 2203823. [Google Scholar] [CrossRef] [PubMed]
  23. DeVita, V.T.; Chu, E. A history of cancer chemotherapy. Cancer Res. 2008, 68, 8643–8653. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  24. Park, W.; Chawla, A.; O’Reilly, E.M. Pancreatic cancer: A review. JAMA 2021, 326, 851–862. [Google Scholar] [CrossRef]
  25. Volker, S. From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment (Review). Int. J. Oncol. 2019, 54, 407–419. [Google Scholar] [CrossRef]
  26. Annovazzi, L.; Mellai, M.; Schiffer, D. Chemotherapeutic drugs: DNA damage and repair in glioblastoma. Cancers 2017, 9, 57. [Google Scholar] [CrossRef] [Green Version]
  27. Kumar, A.; Jaitak, V. Natural products as multidrug resistance modulators in cancer. Eur. J. Med. Chem. 2019, 176, 268–291. [Google Scholar] [CrossRef]
  28. Waghray, D.; Zhang, Q. Inhibit or evade multidrug resistance P-glycoprotein in cancer treatment. J. Med. Chem. 2018, 61, 5108–5121. [Google Scholar] [CrossRef] [PubMed]
  29. Bukowski, K.; Kciuk, M.; Kontek, R. Mechanisms of multidrug resistance in cancer chemotherapy. Int. J. Mol. Sci. 2020, 21, 3233. [Google Scholar] [CrossRef]
  30. Nanayakkara, A.K.; Follit, C.A.; Chen, G.; Williams, N.S.; Vogel, P.D.; Wise, J.G. Targeted inhibitors of P-glycoprotein increase chemotherapeutic-induced mortality of multidrug resistant tumor cells. Sci. Rep. 2018, 8, 967. [Google Scholar] [CrossRef] [Green Version]
  31. Saraswathy, M.; Gong, S. Different strategies to overcome multidrug resistance in cancer. Biotechnol. Adv. 2013, 31, 1397–1407. [Google Scholar] [CrossRef]
  32. Gong, N.; Sheppard, N.C.; Billingsley, M.M.; June, C.H.; Mitchell, M.J. Nanomaterials for T-cell cancer immunotherapy. Nat. Nanotechnol. 2021, 16, 25–36. [Google Scholar] [CrossRef] [PubMed]
  33. Mercan, D.A.; Niculescu, A.G.; Grumezescu, A.M. Nanoparticles for antimicrobial agents delivery—An up-to-date review. Int. J. Mol. Sci. 2022, 23, 13862. [Google Scholar] [CrossRef] [PubMed]
  34. Zashikhina, N.; Gladnev, S.; Sharoyko, V.; Korzhikov-Vlakh, V.; Korzhikova-Vlakh, E.; Tennikova, T. Synthesis and characterization of nanoparticle-based dexamethasone-polypeptide conjugates as potential intravitreal delivery systems. Int. J. Mol. Sci. 2023, 24, 3702. [Google Scholar] [CrossRef] [PubMed]
  35. Busa, P.; Kankala, R.K.; Deng, J.-P.; Liu, C.-L.; Lee, C.-H. Conquering cancer multi-drug resistance using curcumin and cisplatin prodrug-encapsulated mesoporous silica nanoparticles for synergistic chemo- and photodynamic therapies. Nanomaterials 2022, 12, 3693. [Google Scholar] [CrossRef] [PubMed]
  36. Muniyandi, P.; Palaninathan, V.; Hanajiri, T.; Maekawa, T. Direct cardiac epigenetic reprogramming through codelivery of 5′azacytidine and miR-133a nanoformulation. Int. J. Mol. Sci. 2022, 23, 15179. [Google Scholar] [CrossRef] [PubMed]
  37. Nezhadi, S.; Dorkoosh, F. Co-delivery systems: Hope for clinical application? Drug Deliv. Transl. Res. 2022, 12, 1339–1354. [Google Scholar] [CrossRef]
  38. Sahrayi, H.; Hosseini, E.; Karimifard, S.; Khayam, N.; Meybodi, S.M.; Amiri, S.; Bourbour, M.; Farasati Far, B.; Akbarzadeh, I.; Bhia, M.; et al. Co-Delivery of letrozole and cyclophosphamide via folic acid-decorated nanoniosomes for breast cancer therapy: Synergic effect, augmentation of cytotoxicity, and apoptosis gene expression. Pharmaceuticals 2022, 15, 6. [Google Scholar] [CrossRef]
  39. Enserink, M.; Hines, P.; Vignieri, S.; Wigginton, N.; Yeston, J. The pesticide paradox. Science 2013, 341, 728–729. [Google Scholar] [CrossRef] [Green Version]
  40. Kaur, R.; Mavi, G.K.; Raghav, S. Pesticides classification and its impact on environment. Int. J. Curr. Microbiol. Appl. Sci. 2019, 8, 1889–1897. [Google Scholar] [CrossRef]
  41. Tudi, M.; Ruan, H.D.; Wang, L.; Lyu, J.; Sadler, R.; Connell, D.; Chu, C.; Phung, D.T. Agriculture development, pesticide application and its impact on the environment. Int. J. Environ. Res. Public Health 2021, 18, 1112. [Google Scholar] [CrossRef]
  42. Kah, M.; Beulke, S.; Tiede, K.; Hofmann, T. Nanopesticides: State of knowledge, environmental fate, and exposure modeling. Crit. Rev. Environ. Sci. Technol. 2013, 43, 1823–1867. [Google Scholar] [CrossRef]
  43. Kah, M.; Hofmann, T. Nanopesticide research: Current trends and future priorities. Environ. Int. 2014, 63, 224–235. [Google Scholar] [CrossRef] [PubMed]
  44. Wais, U.; Jackson, A.W.; He, T.; Zhang, H. Nanoformulation and encapsulation approaches for poorly water-soluble drug nanoparticles. Nanoscale 2016, 8, 1746–1769. [Google Scholar] [CrossRef] [PubMed]
  45. Mattos, B.D.; Tardy, B.L.; Magalhães, W.L.E.; Rojas, O.J. Controlled release for crop and wood protection: Recent progress toward sustainable and safe nanostructured biocidal systems. J. Control. Release 2017, 262, 139–150. [Google Scholar] [CrossRef] [PubMed]
  46. Chhipa, H. Nanofertilizers and nanopesticides for agriculture. Environ. Chem. Lett. 2017, 15, 15–22. [Google Scholar] [CrossRef]
  47. Deka, B.; Babu, A.; Baruah, C.; Barthakur, M. Nanopesticides: A systematic review of their prospects with special reference to tea pest management. Front. Nutr. 2021, 8, 686131. [Google Scholar] [CrossRef]
  48. Wang, D.; Saleh, N.B.; Byro, A.; Zepp, R.; Sahle-Demessie, E.; Luxton, T.P.; Ho, K.T.; Burgess, R.M.; Flury, M.; White, J.C.; et al. Nano-enabled pesticides for sustainable agriculture and global food security. Nat. Nanotechnol. 2022, 17, 347–360. [Google Scholar] [CrossRef]
  49. Jurczyk, M.; Kasperczyk, J.; Wrześniok, D.; Beberok, A.; Jelonek, K. Nanoparticles loaded with docetaxel and resveratrol as an advanced tool for cancer therapy. Biomedicines 2022, 10, 1187. [Google Scholar] [CrossRef]
  50. Khafaji, M.; Zamani, M.; Vossoughi, M.; Zad, A.I. Doxorubicin/cisplatin-loaded superparamagnetic nanoparticles as a stimuli-responsive co-delivery system for chemo-photothermal therapy. Int. J. Nanomed. 2019, 14, 8769–8786. [Google Scholar] [CrossRef] [Green Version]
  51. Nechaeva, A.; Artyukhov, A.; Luss, A.; Shtilman, M.; Gritskova, I.; Shulgin, A.; Motyakin, M.; Levina, I.; Krivoborodov, E.; Toropygin, I.; et al. Synthesis of amphiphilic copolymers of N-Vinyl-2-pyrrolidone and allyl glycidyl ether for co-delivery of doxorubicin and paclitaxel. Polymers 2022, 14, 1727. [Google Scholar] [CrossRef]
  52. Alven, S.; Aderibigbe, B.A. Efficacy of polymer-based nanocarriers for co-delivery of curcumin and selected anticancer drugs. Nanomaterials 2020, 10, 1556. [Google Scholar] [CrossRef] [PubMed]
  53. Ataide, J.A.; Coco, J.C.; dos Santos, É.M.; Beraldo-Araujo, V.; Silva, J.R.A.; de Castro, K.C.; Lopes, A.M.; Filipczak, N.; Yalamarty, S.S.K.; Torchilin, V.P.; et al. Co-encapsulation of drugs for topical application—A review. Molecules 2023, 28, 1449. [Google Scholar] [CrossRef] [PubMed]
  54. Chao, X.; Yu, S.; Liu, L.; Wu, X.; Dai, H. Magnetically targeted co-delivery of hydrophilic and hydrophobic drugs with hollow mesoporous ferrite nanoparticles. RSC Adv. 2018, 8, 15326. [Google Scholar] [CrossRef] [Green Version]
  55. Chen, D.; Wang, G.; Song, W.; Zhang, Q. Novel CD44 receptor targeting multifunctional “nano-eggs” based on double pH-sensitive nanoparticles for co-delivery of curcumin and paclitaxel to cancer cells and cancer stem cells. J. Nanopart. Res. 2015, 17, 421. [Google Scholar] [CrossRef]
  56. Karimifard, S.; Rezaei, N.; Jamshidifar, E.; Langeroodi, S.M.F.; Abdihaji, M.; Mansouri, A.; Hosseini, M.; Ahmadkhani, N.; Rahmati, Z.; Heydari, M.; et al. pH-responsive chitosan-adorned niosome nanocarriers for co-delivery of drugs for breast cancer therapy. ACS Appl. Nano Mater. 2022, 5, 8811–8825. [Google Scholar] [CrossRef]
  57. Zhang, D.; Kong, Y.; Sun, J.; Huo, S.; Zhou, M.; Gui, Y.; Mu, X.; Chen, H.; Yu, S.; Xu, Q. Co-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance. Int. J. Nanomed. 2017, 12, 2081–2108. [Google Scholar] [CrossRef] [Green Version]
  58. Tian, F.; Dahmani, F.Z.; Qiao, J.; Ni, J.; Xiong, H.; Liu, T.; Zhou, J.; Yao, J. A targeted nanoplatform co-delivering chemotherapeutic and antiangiogenic drugs as a tool to reverse multidrug resistance in breast cancer. Acta Biomater. 2018, 75, 398–412. [Google Scholar] [CrossRef]
  59. Hu, Q.; Shang, L.; Wang, M.; Tu, K.; Hu, M.; Yu, Y.; Xu, M.; Kong, L.; Guo, Y.; Zhang, Z. Co-delivery of paclitaxel and interleukin-12 regulating tumor microenvironment for cancer immunochemotherapy. Adv. Healthc. Mater. 2020, 9, 1901858. [Google Scholar] [CrossRef]
  60. Ultimo, A.; Orzaez, M.; Santos-Martinez, M.J.; Martínez-Máñez, R.; Marcos, M.D.; Sancenón, F.; Ruiz-Hernández, E. High-capacity mesoporous silica nanocarriers of siRNA for applications in retinal delivery. Int. J. Mol. Sci. 2023, 24, 2753. [Google Scholar] [CrossRef]
  61. Abashkin, V.; Pędziwiatr-Werbicka, E.; Horodecka, K.; Zhogla, V.; Ulashchik, E.; Shmanai, V.; Shcharbin, D.; Bryszewska, M. Silver nanoparticles modified by carbosilane dendrons and PEG as delivery vectors of small interfering RNA. Int. J. Mol. Sci. 2023, 24, 840. [Google Scholar] [CrossRef]
  62. Zare, M.; Pemmada, R.; Madhavan, M.; Shailaja, A.; Ramakrishna, S.; Kandiyil, S.P.; Donahue, J.M.; Thomas, V. Encapsulation of miRNA and siRNA into nanomaterials for cancer therapeutics. Pharmaceutics 2022, 14, 1620. [Google Scholar] [CrossRef] [PubMed]
  63. Tabernero, J.; Shapiro, J.I.; LoRusso, P.M.; Cervantes, A.; Schwartz, G.K.; Weiss, G.J.; Paz-Ares, L.; Cho, D.C.; Infante, J.R.; Alsina, M.; et al. First-in-humans trial of an RNA interference therapeutic targeting VEGF and KSP in cancer patients with liver involvement. Cancer Discov. 2013, 3, 406–417. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  64. Ball, R.L.; Hajj, K.A.; Vizelman, J.; Bajaj, P.; Whitehead, K.A. Lipid nanoparticle formulations for enhanced co-delivery of siRNA and mRNA. Nano Lett. 2018, 18, 3814–3822. [Google Scholar] [CrossRef] [PubMed]
  65. Yang, C.; Chan, K.K.; Lin, W.J.; Soehartono, A.M.; Lin, G.; Toh, H.; Yoon, H.S.; Chen, C.K.; Yong, K.T. Biodegradable nanocarriers for small interfering ribonucleic acid (siRNA) co-delivery strategy increase the chemosensitivity of pancreatic cancer cells to gemcitabine. Nano Res. 2017, 10, 3049–3067. [Google Scholar] [CrossRef]
  66. Wang, Y.; Wu, Q.; Wang, J.; Li, L.; Sun, X.; Zhang, Z.; Zhang, L. Co-delivery of p38α MAPK and p65 siRNA by novel liposomal glomerulus-targeting nano carriers for effective immunoglobulin a nephropathy treatment. J. Control. Release 2020, 320, 457–468. [Google Scholar] [CrossRef]
  67. Park, H.; Oh, J.; Shim, G.; Cho, B.; Chang, Y.; Kim, S.; Baek, S.; Kim, H.; Shin, J.; Choi, H.; et al. In vivo neuronal gene editing via CRISPR–Cas9 amphiphilic nanocomplexes alleviates deficits in mouse models of Alzheimer’s disease. Nat. Neurosci. 2019, 22, 524–528. [Google Scholar] [CrossRef]
  68. Lee, B.; Lee, K.; Panda, S.; Gonzales-Rojas, R.; Chong, A.; Bugay, V.; Park, H.M.; Brenner, R.; Murthy, N.; Lee, H.Y. Nanoparticle delivery of CRISPR into the brain rescues a mouse model of fragile X syndrome from exaggerated repetitive behaviours. Nat. Biomed. Eng. 2018, 2, 497–507. [Google Scholar] [CrossRef]
  69. Wei, T.; Cheng, Q.; Farbiak, L.; Anderson, D.G.; Langer, R.; Siegwart, D.J. Delivery of tissue-targeted scalpels: Opportunities and challenges for in vivo CRISPR/Cas-based genome editing. ACS Nano 2020, 14, 9243–9262. [Google Scholar] [CrossRef]
  70. Wang, H.X.; Song, Z.; Lao, Y.H.; Xu, X.; Gong, J.; Cheng, D.; Chakraborty, S.; Park, J.S.; Li, M.; Huang, D.; et al. Nonviral gene editing via CRISPR/Cas9 delivery by membrane-disruptive and endosomolytic helical polypeptide. Proc. Natl. Acad. Sci. USA 2018, 115, 4903–4908. [Google Scholar] [CrossRef] [Green Version]
  71. Sriram, V.; Lee, J.Y. Calcium phosphate-polymeric nanoparticle system for co-delivery of microRNA-21 inhibitor and doxorubicin. Colloids Surf. B 2021, 208, 112061. [Google Scholar] [CrossRef]
  72. Fischer, T.; Winter, I.; Drumm, R.; Schneider, M. Cylindrical microparticles composed of mesoporous silica nanoparticles for the targeted delivery of a small molecule and a macromolecular drug to the lungs: Exemplified with curcumin and siRNA. Pharmaceutics 2021, 13, 844. [Google Scholar] [CrossRef]
  73. Tabatabaei, S.N.; Derbali, R.M.; Yang, C.; Superstein, R.; Hamel, P.; Chain, J.L.; Hardy, P. Co-delivery of miR-181a and melphalan by lipid nanoparticles for treatment of seeded retinoblastoma. J. Control. Release 2019, 298, 177–185. [Google Scholar] [CrossRef] [PubMed]
  74. Zhang, R.; Wei, S.; Shao, L.; Tong, L.; Wu, Y. Imaging intracellular drug/siRNA co-delivery by self-sssembly cross-linked polyethylenimine with fluorescent core-shell silica nanoparticles. Polymers 2022, 14, 1813. [Google Scholar] [CrossRef] [PubMed]
  75. Biswas, S.; Deshpande, P.P.; Navarro, G.; Dodwadkar, N.S.; Torchilin, V.P. Lipid modified triblock PAMAM-based nanocarriers for siRNA drug co-delivery. Biomaterials 2013, 34, 1289–1301. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  76. Zhang, C.G.; Zhu, W.J.; Liu, Y.; Yuan, Z.Q.; Yang, S.D.; Chen, W.L.; Li, J.Z.; Zhou, X.F.; Liu, C.; Zhang, X.N. Novel polymer micelle mediated co-delivery of doxorubicin and P-glycoprotein siRNA for reversal of multidrug resistance and synergistic tumor therapy. Sci. Rep. 2016, 6, 23859. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  77. Joshi, U.; Filipczak, N.; Khan, M.M.; Attia, S.A.; Torchilin, V. Hypoxia-sensitive micellar nanoparticles for co-delivery of siRNA and chemotherapeutics to overcome multi-drug resistance in tumor cells. Int. J. Pharm. 2020, 590, 119915. [Google Scholar] [CrossRef]
  78. Guo, X.; Fang, Z.; Zhang, M.; Yang, D.; Wang, S.; Liu, K. A co-delivery system of curcumin and p53 for enhancing the sensitivity of drug-resistant ovarian cancer cells to cisplatin. Molecules 2020, 25, 2621. [Google Scholar] [CrossRef]
  79. Chen, W.; Zhang, M.; Shen, W.; Du, B.; Yang, J.; Zhang, Q. A polycationic brush mediated co-delivery of doxorubicin and gene for combination therapy. Polymers 2019, 11, 60. [Google Scholar] [CrossRef] [Green Version]
  80. Zhao, S.; Huang, W.; Wang, C.; Wang, Y.; Zhang, Y.; Ye, Z.; Zhang, J.; Deng, L.; Dong, A. Screening and matching amphiphilic cationic polymers for efficient antibiosis. Biomacromolecules 2020, 21, 5269–5281. [Google Scholar] [CrossRef]
  81. Ahmad, M.M.; Mushtaq, S.; Al Qahtani, H.S.; Sedky, A.; Alam, M.W. Investigation of TiO2 nanoparticles synthesized by Sol-Gel method for effectual photodegradation, oxidation and reduction Reaction. Crystals 2021, 11, 1456. [Google Scholar] [CrossRef]
  82. Wahid, I.; Rani, P.; Kumari, S.; Ahmad, R.; Hussain, S.J.; Alamri, S.; Tripathy, N.; Khan, M.R. Biosynthesized gold nanoparticles maintained nitrogen metabolism, nitric oxide synthesis, ions balance, and stabilizes the defense systems to improve salt stress tolerance in wheat. Chemosphere 2022, 287, 132142. [Google Scholar] [CrossRef]
  83. Ayoub, H.A.; Khairy, M.; Elsaid, S.; Rashwan, F.A.; Abdel-Hafez, H.F. Pesticidal activity of nanostructured metal oxides for generation of alternative pesticide formulations. J. Agric. Food Chem. 2018, 66, 5491–5498. [Google Scholar] [CrossRef] [PubMed]
  84. Bharani, R.S.A.; Namasivayam, S.K.R. Biogenic silver nanoparticles mediated stress on developmental period and gut physiology of major lepidopteran pest Spodoptera litura (Fab.) (Lepidoptera: Noctuidae)—An eco-friendly approach of insect pest control. J. Environ. Chem. Eng. 2017, 5, 453–467. [Google Scholar] [CrossRef]
  85. Kumari, M.; Pandey, S.; Bhattacharya, A.; Mishra, A.; Nautiyal, C.S. Protective role of biosynthesized silver nanoparticles against early blight disease in Solanum lycopersicum. Plant Physiol. Biochem. 2017, 121, 216–225. [Google Scholar] [CrossRef] [PubMed]
  86. Mustafa, I.F.; Hussein, M.Z. Synthesis and technology of nanoemulsion-based pesticide formulation. Nanomaterials 2020, 10, 1608. [Google Scholar] [CrossRef]
  87. Adisa, I.O.; Pullagurala, V.L.R.; Peralta-Videa, J.R.; Dimkpa, C.O.; Elmer, W.H.; Gardea-Torresdey, J.L.; White, J.C. Recent advances in nano-enabled fertilizers and pesticides: A critical review of mechanisms of action. Environ. Sci. Nano 2019, 6, 2002. [Google Scholar] [CrossRef]
  88. Guleria, G.; Thakur, S.; Shandiiya, M.; Sharma, S.; Thakur, S.; Kalia, S. Nanotechnology for sustainable agro-food systems: The need and role of nanoparticles in protecting plants and improving crop productivity. Plant Physiol. Biochem. 2023, 194, 533–549. [Google Scholar] [CrossRef]
  89. Jiang, Q.; Xie, Y.; Peng, M.; Wang, Z.; Li, T.; Yin, M.; Shen, J.; Yan, S. Nanocarrier-pesticide delivery system with promising benefits in a case of dinotefuran: Strikingly enhanced bioactivity and reduced pesticide residue. Environ. Sci. Nano 2022, 9, 988–999. [Google Scholar] [CrossRef]
  90. Rastogi, A.; Tripathi, D.K.; Yadav, S.; Chauhan, D.K.; Živčák, M.; Ghorbanpour, M.; El-Sheery, N.I.; Brestic, M. Application of silicon nanoparticles in agriculture. 3 Biotech 2019, 9, 90. [Google Scholar] [CrossRef] [Green Version]
  91. Naaz, H.; Rawat, K.; Saffeullah, P.; Umar, S. Silica nanoparticles synthesis and applications in agriculture for plant fertilization and protection: A review. Environ. Chem. Lett. 2022, 21, 539–559. [Google Scholar] [CrossRef]
  92. Li, W.; Fan, R.; Zhou, H.; Zhu, Y.; Zheng, X.; Tang, M.; Wu, X.; Yu, C.; Wang, G. Improving the utilization rate of foliar nitrogen fertilizers by surface roughness engineering of silica spheres. Environ. Sci. Nano 2020, 7, 3526–3535. [Google Scholar] [CrossRef]
  93. Zhu, F.; Liu, X.; Cao, L.; Cao, C.; Li, F.; Chen, C.; Xu, C.; Huang, Q.; Du, F. Uptake and distribution of fenoxanil-loaded mesoporous silica nanoparticles in rice plants. Int. J. Mol. Sci. 2018, 19, 2854. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  94. Zakeri, A.; Kouhbanani, M.A.J.; Beheshtkhoo, N.; Beigi, V.; Mousavi, S.M.; Hashemi, S.A.M.; Zade, A.K.; Amani, A.M.; Savardashtaki, A.; Mirzaei, E.; et al. Polyethylenimine-based nanocarriers in co-delivery of drug and gene: A developing horizon. Nano Rev. Exp. 2018, 9, 1488497. [Google Scholar] [CrossRef] [Green Version]
  95. Yan, S.; Hu, Q.; Li, J.; Chao, Z.; Cai, C.; Yin, M.; Du, X.; Shen, J. A star polycation acts as a drug nanocarrier to improve the toxicity and persistence of botanical pesticides. ACS Sustain. Chem. Eng. 2019, 7, 17406–17413. [Google Scholar] [CrossRef]
  96. Yan, S.; Hu, Q.; Jiang, Q.; Chen, H.; Wei, J.; Yin, M.; Du, X.; Shen, J. Simple osthole/nanocarrier pesticide efficiently controls both pests and diseases fulfilling the need of green production of strawberry. ACS Appl. Mater. Interfaces 2021, 13, 36350–36360. [Google Scholar] [CrossRef]
  97. Yan, S.; Hu, Q.; Wei, Y.; Jiang, Q.; Yin, M.; Dong, M.; Shen, J.; Du, X. Calcium nutrition nanoagent rescues tomatoes from mosaic virus disease by accelerating calcium transport and activating antiviral immunity. Front. Plant Sci. 2022, 13, 1092774. [Google Scholar] [CrossRef] [PubMed]
  98. Wang, X.; Zheng, K.; Cheng, W.; Li, J.; Liang, X.; Shen, J.; Dou, D.; Yin, M.; Yan, S. Field application of star polymer-delivered chitosan to amplify plant defense against potato late blight. Chem. Eng. J. 2021, 417, 129327. [Google Scholar] [CrossRef]
  99. Camara, M.C.; Campos, E.V.R.; Monteiro, R.A.; Pereira, A.E.S.; Proenca, P.L.F.; Fraceto, L.F. Development of stimuli-responsive nano-based pesticides: Emerging opportunities for agriculture. J. Nanobiotechnol. 2019, 17, 100. [Google Scholar] [CrossRef] [Green Version]
  100. Liu, B.; Chen, C.; Teng, G.; Tian, G.; Zhang, G.; Gao, Y.; Zhang, L.; Wu, Z.; Zhang, J. Chitosan- based organic/inorganic composite engineered for UV light-controlled smart pH-responsive pesticide through in situ photo-induced generation of acid. Pest Manag. Sci. 2022, 78, 2299–2308. [Google Scholar] [CrossRef]
  101. Ren, L.; Hao, B.; Fang, W.; Zhang, D.; Cheng, H.; Li, Q.; Yan, D.; Li, Y.; Wang, Q.; Zhou, Z.; et al. Combination of modified biochar and polyurea microcapsules to co-encapsulate a fumigant via interface polymerization for controlled release and enhanced bioactivity. Pest Manag. Sci. 2021, 78, 73–85. [Google Scholar] [CrossRef]
  102. Ray, P.; Sahu, D.; Aminedi, R.; Chandran, D. Concepts and considerations for enhancing RNAi efficiency in phytopathogenic fungi for RNAi-based crop protection using nanocarrier-mediated dsRNA delivery systems. Front. Fungal Bio. 2022, 3, 977502. [Google Scholar] [CrossRef]
  103. Akbar, S.; Wei, Y.; Zhang, M.-Q. RNA Interference: Promising approach to combat plant viruses. Int. J. Mol. Sci. 2022, 23, 5312. [Google Scholar] [CrossRef]
  104. Menezes, P.S.; Yan, Y.; Yang, Y.; Mitter, N.; Mahony, T.J.; Mody, K.T. RNAi-based biocontrol of pests to improve the productivity and welfare of livestock production. Appl. Biosci. 2022, 1, 229–243. [Google Scholar] [CrossRef]
  105. Gurusamy, D.; Mogilicherla, K.; Shukla, J.N.; Palli, S.R. Lipids help double-stranded RNA in endosomal escape and improve RNA interference in the fall armyworm, Spodoptera frugiperda. Arch. Insect Biochem. Physiol. 2020, 104, e21678. [Google Scholar] [CrossRef] [PubMed]
  106. Ma, Z.; Zheng, Y.; Chao, Z.; Chen, H.; Zhang, Y.; Yin, M.; Shen, J.; Yan, S. Visualization of the process of a nanocarrier-mediated gene delivery: Stabilization, endocytosis and endosomal escape of genes for intracellular spreading. J. Nanobiotechnol. 2022, 20, 124. [Google Scholar] [CrossRef] [PubMed]
  107. He, B.; Chu, Y.; Yin, M.; Müllen, K.; An, C.; Shen, J. Fluorescent nanoparticle delivered dsRNA toward genetic control of insect pests. Adv. Mater. 2013, 25, 4580–4584. [Google Scholar] [CrossRef]
  108. Lu, Q.; Cui, H.; Li, W.; Liu, T.; Chen, Q.; Qing, Y. Synthetic nanoscale RNAi constructs as pesticides for the control of Locust migratoria. J. Agric. Food Chem. 2022, 70, 10762–10770. [Google Scholar] [CrossRef]
  109. Zhang, Y.; Ma, Z.Z.; Zhou, H.; Chao, Z.J.; Yan, S.; Shen, J. Nanocarrier-delivered dsRNA suppresses wing development of green peach aphids. Insect Sci. 2022, 29, 669–682. [Google Scholar] [CrossRef]
  110. Hoang, B.T.L.; Fletcher, S.J.; Brosnan, C.A.; Ghodke, A.B.; Manzie, N.; Mitter, N. RNAi as a foliar spray: Efficiency and challenges to field applications. Int. J. Mol. Sci. 2022, 23, 6639. [Google Scholar] [CrossRef]
  111. Kiselev, K.V.; Suprun, A.R.; Aleynova, O.A.; Ogneva, Z.V.; Dubrovina, A.S. Physiological conditions and dsRNA application approaches for exogenously induced RNA interference in arabidopsis thaliana. Plants 2021, 10, 264. [Google Scholar] [CrossRef]
  112. Zotti, M.; Santos, E.A.D.; Cagliari, D.; Christiaens, O.; Taning, C.N.T.; Smagghe, G. RNA interference technology in crop protection against arthropod pests, pathogens and nematodes. Pest Manag. Sci. 2018, 74, 1239–1250. [Google Scholar] [CrossRef] [PubMed]
  113. Majumdar, S.; Keller, A.A. Omics to address the opportunities and challenges of nanotechnology in agriculture. Crit. Rev. Environ. Sci. Technol. 2021, 51, 2595–2636. [Google Scholar] [CrossRef]
  114. Wang, M.; Jin, H. Spray-induced gene silencing: A powerful innovative strategy for crop protection. Trends Microbiol. 2017, 25, 4–6. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  115. Zheng, Y.; Hu, Y.; Yan, S.; Zhou, H.; Song, D.; Yin, M.; Shen, J. A polymer/detergent formulation improves dsRNA penetration through the body wall and RNAi-induced mortality in the soybean aphid Aphis glycines. Pest Manag. Sci. 2019, 75, 1993–1999. [Google Scholar] [CrossRef]
  116. Yan, S.; Qian, J.; Cai, C.; Ma, Z.; Li, J.; Yin, M.; Ren, B.; Shen, J. Spray method application of transdermal dsRNA delivery system for efficient gene silencing and pest control on soybean aphid Aphis glycines. J. Pest Sci. 2020, 93, 449–459. [Google Scholar] [CrossRef]
  117. Ma, Z.; Zhang, Y.; Li, M.; Chao, Z.; Du, X.; Yan, S.; Shen, J. A first greenhouse application of bacteria-expressed and nanocarrier-delivered RNA pesticide for Myzus persicae control. J. Pest Sci. 2022, 96, 181–193. [Google Scholar] [CrossRef]
  118. Yang, J.; Yan, S.; Xie, S.; Yin, M.; Shen, J.; Li, Z.; Zhou, Y.; Duan, L. Construction and application of star polycation nanocarrier-based microRNA delivery system in Arabidopsis and maize. J. Nanobiotechnol. 2022, 20, 219. [Google Scholar] [CrossRef]
  119. Lyu, Z.; Xiong, M.; Mao, J.; Li, W.; Jiang, G.; Zhang, W. A dsRNA delivery system based on the rosin-modified polyethylene glycol and chitosan induces gene silencing and mortality in Nilaparvata lugens. Pest Manag. Sci. 2022; online ahead of print. [Google Scholar] [CrossRef]
  120. Guo, H.; Liu, X.-Z.; Long, G.-J.; Gong, L.-L.; Zhang, M.-Q.; Ma, Y.-F.; Hull, J.J.; Dewer, Y.; He, M.; He, P. Functional characterization of developmentally critical genes in the white-backed planthopper: Efficacy of nanoparticle-based dsRNA sprays for pest control. Pest Manag. Sci. 2023, 79, 1048–1061. [Google Scholar] [CrossRef]
  121. Kolge, H.; Kadam, K.; Galande, S.; Lanjekar, V.; Ghormade, V. New frontiers in pest control: Chitosan nanoparticles-shielded dsRNA as an effective topical RNAi spray for gram podborer biocontrol. ACS Appl. Bio. Mat. 2021, 4, 5145–5157. [Google Scholar] [CrossRef]
  122. Gurusamy, D.; Mogilicherla, K.; Palli, S.R. Chitosan nanoparticles help double-stranded RNA escape from endosomes and improve RNA interference in the fall armyworm, Spodoptera frugiperda. Arch. Insect Biochem. Physiol. 2020, 104, e21677. [Google Scholar] [CrossRef] [PubMed]
  123. Castellanos, N.L.; Smagghe, G.; Sharma, R.; Oliveira, E.E.; Christiaens, O. Liposome encapsulation and EDTA formulation of dsRNA targeting essential genes increase oral RNAi-caused mortality in the Neotropical stink bug Euschistus heros. Pest Manag. Sci. 2019, 75, 537–548. [Google Scholar] [CrossRef] [PubMed]
  124. Lin, Y.H.; Huang, J.H.; Liu, Y.; Belles, X.; Lee, H.J. Oral delivery of dsRNA lipoplexes to German cockroach protects dsRNA from degradation and induces RNAi response. Pest Manag. Sci. 2017, 73, 960–966. [Google Scholar] [CrossRef] [PubMed]
  125. Wang, K.; Peng, Y.; Chen, J.; Peng, Y.; Wang, X.; Shen, Z.; Han, Z. Comparison of efficacy of RNAi mediated by various nanoparticles in the rice striped stem borer (Chilo suppressalis). Pestic. Biochem. Physiol. 2019, 165, 104467. [Google Scholar] [CrossRef] [PubMed]
  126. Islam, M.T.; Davis, Z.; Chen, L.; Englaender, J.; Zomorodi, S.; Frank, J.; Bartlett, K.; Somers, E.; Carballo, S.M.; Kester, M.; et al. Minicell-based fungal RNAi delivery for sustainable crop protection. Microb. Biotechnol. 2021, 14, 1847–1856. [Google Scholar] [CrossRef]
  127. Qiao, L.; Niño-Sánchez, J.; Hamby, R.; Capriotti, L.; Chen, A.; Mezzetti, B.; Jin, H. Artificial nanovesicles for dsRNA delivery in spray-induced gene silencing for crop protection. Plant Biotechnol. J. 2023; online ahead of print. [Google Scholar] [CrossRef]
  128. Mitter, N.; Worrall, E.A.; Robinson, K.E.; Jain, R.G.; Taochy, C.; Fletcher, S.J.; Carroll, B.J.; Lu, G.Q.; Xu, Z.P. Clay nanosheets for topical delivery of RNAi for sustained protection against plant viruses. Nat. Plants 2017, 3, 16207. [Google Scholar] [CrossRef]
  129. Worrall, E.A.; Bravo-Cazar, A.; Nilon, A.T.; Fletcher, S.J.; Robinson, K.E.; Carr, J.P.; Mitter, N. Exogenous application of RNAi-inducing double-stranded RNA inhibits aphid-mediated transmission of a plant virus. Front. Plant Sci. 2019, 10, 265. [Google Scholar] [CrossRef] [Green Version]
  130. Duanis-Assaf, D.; Shlar, I.; Galsurker, O.; Davydov, O.; Maurer, D.; Feygenberg, O.; Poverenov, E.; Fluhr, R.; Alkan, N. Nano-clay, layered-double hydroxide (LDH), improves the efficacy of double-stranded RNA in controlling postharvest decay. Postharvest Biol. Technol. 2022, 193, 112051. [Google Scholar] [CrossRef]
  131. Chen, X.; Shi, T.; Tang, T.; Chen, C.; Liang, Y.; Zuo, S. Nanosheet-facilitated spray delivery of dsRNAs represents a potential tool to control Rhizoctonia solani infection. Int. J. Mol. Sci. 2022, 23, 12922. [Google Scholar] [CrossRef]
  132. Niño-Sánchez, J.; Sambasivam, P.T.; Sawyer, A.; Hamby, R.; Chen, A.; Czislowski, E.; Li, P.; Manzie, N.; Gardiner, D.M.; Ford, R.; et al. BioClay™ prolongs RNA interference-mediated crop protection against Botrytis cinereal. J. Integr. Plant Biol. 2022, 64, 2027–2211. [Google Scholar] [CrossRef] [PubMed]
  133. Suraphan, N.; Fan, L.; Liu, B.; Wu, D. Co-delivery of chlorantraniliprole and avermectin with a polylactide microcapsule formulation. RSC Adv. 2020, 10, 25418. [Google Scholar] [CrossRef] [PubMed]
  134. Li, M.; Ma, Z.; Peng, M.; Li, L.; Yin, M.; Yan, S.; Shen, J. A gene and drug co-delivery application helps to solve the short life disadvantage of RNA drug. Nano Today 2022, 43, 101452. [Google Scholar] [CrossRef]
  135. Qu, X.; Wang, S.; Lin, G.; Li, M.; Shen, J.; Wang, D. The synergistic effect of thiamethoxam and synapsin dsRNA targets neurotransmission to induce mortality in Aphis gossypii. Int. J. Mol. Sci. 2022, 23, 9388. [Google Scholar] [CrossRef]
  136. Shao, C.; Zhao, H.; Wang, P. Recent development in functional nanomaterials for sustainable and smart agricultural chemical technologies. Nano Converg. 2022, 9, 11. [Google Scholar] [CrossRef]
  137. Pandhi, S.; Mahato, D.K.; Kumar, A. Overview of green nanofabrication technologies for food quality and safety applications. Food Rev. Int. 2021, 37, 1–21. [Google Scholar] [CrossRef]
  138. Al Bostami, R.D.; Abuwatfa, W.H.; Husseini, G.A. Recent advances in nanoparticle-based co-delivery systems for cancer therapy. Nanomaterials 2022, 12, 2672. [Google Scholar] [CrossRef]
  139. Coslor, C.C.; Sundin, G.W.; Wise, J.C. The efficacy of trunk injections of emamectin benzoate and phosphorous acid for control of obliquebanded leafroller and apple scab on semi-dwarf apple. Crop Prot. 2019, 118, 44–49. [Google Scholar] [CrossRef]
  140. Fumoto, S.; Nishida, K. Co-Delivery systems of multiple drugs using nanotechnology for future cancer therapy. Chem. Pharm. Bull. 2020, 68, 603–612. [Google Scholar] [CrossRef]
  141. Tang, S.; Yin, Q.; Zhang, Z.; Gu, W.; Chen, L.; Yu, H.; Huang, Y.; Chen, X.; Xu, M.; Li, Y. Co-delivery of doxorubicin and RNA using pH-sensitive poly (β-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer. Biomaterials 2014, 35, 6047–6059. [Google Scholar] [CrossRef]
  142. Dong, M.; Chen, D.; Che, L.; Gu, N.; Yin, M.; Du, X.; Shen, J.; Yan, S. Biotoxicity evaluation of a cationic star polymer on a predatory ladybird and cooperative pest control by polymer-delivered pesticides and ladybird. ACS Appl. Mater. Interfaces 2022, 14, 6083–6092. [Google Scholar] [CrossRef] [PubMed]
  143. Yan, S.; Li, N.; Guo, Y.; Chen, Y.; Ji, C.; Yin, M.; Shen, J.; Zhang, J. Chronic exposure to the star polycation (SPc) nanocarrier in the larval stage adversely impairs life history traits in Drosophila melanogaster. J. Nanobiotechnol. 2022, 20, 515. [Google Scholar] [CrossRef] [PubMed]
Ijms 24 05121 g001 550
Figure 1. Combination route and mechanism of co-delivery system. Cargoes (genes or drugs) are encapsulated in nanoparticles, and then delivered into the cytoplasm through endosomal escape.
Figure 1. Combination route and mechanism of co-delivery system. Cargoes (genes or drugs) are encapsulated in nanoparticles, and then delivered into the cytoplasm through endosomal escape.
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Ijms 24 05121 g002 550
Figure 2. Application of co-delivery system is promising in agricultural field. Fabrication of co-delivery nanopesticide system, assembled with insecticides, fungicides or fertilizers, achieves synergistic effects or multiple aspects of drug administration simultaneously.
Figure 2. Application of co-delivery system is promising in agricultural field. Fabrication of co-delivery nanopesticide system, assembled with insecticides, fungicides or fertilizers, achieves synergistic effects or multiple aspects of drug administration simultaneously.
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Table
Table 1. Applications of NPs-mediated RNA pesticides for insect control.
Table 1. Applications of NPs-mediated RNA pesticides for insect control.
NPsTarget PestTarget GenesEffectsRef.
block copolymerLocust migratoriaLmCHS210% died directly and 15% were unable to walk after molting[108]
cationic dendrimersAphis glycineshemocytin80.5% suppression of population density[115]
polyethylene glycol and chitosanNilaparvata lugenschitin synthetase A65.8% mortality[119]
star polycationMyzus persicaevestigial, ultrabithorax63.3% and 32.2% wing aberration rates[109]
Aphis glycinesTREH, ATPD, ATPE and CHS1high mortality up to 81.67%[116]
Myzus persicaeATP-d, ATP-G61% control efficacy on 3 d[117]
Sogatella furciferaSfEGFR, Sfzfh-2,
SfAbd-A, SfAbd-B		around 70% mortality[120]
chitosanHelicoverpa armigeraJHAMT, ACHE100% mortality[121]
Spodoptera frugiperdaIAP47% mortality[122]
liposomeEuschistus herosV-ATPaseA, Muscle
actin		45% and 42% mortality[123]
Blattella germanicaα-tubulin60% mortality[124]
quantum dotChilo suppressalisG3PDH70% mortality[125]
cerium oxideEuschistus herostroponinabout 80% mortality[20]
Table
Table 2. Applications of NPs-mediated RNA pesticides for plant disease management.
Table 2. Applications of NPs-mediated RNA pesticides for plant disease management.
NPsHostPathogenTarget GenesEffectsRef.
minicellstrawberryBotryotinia fuckelianaChs3a, Chs3b, DCL1, DCL2halted disease progression for 12 days[126]
star polycationriceRhizoctonia solaniRsAGO1, RsAGO2the protection time up to 20 days[5]
nanovesiclestomato,
grape		Botrytis cinereaDicer-like 1, Dicer-like 2extended the protection duration to 10–21 days[127]
layered double hydroxide (LDH)
chitosan		cowpeacommon mosaic virusCMV2bvirus protection for at least 20 days[128]
cowpeabean common mosaic viruscoat proteinprevent infection for spraying 5d in advance[129]
grape,
cherry		Botrytis cinereaerg13, erg11, erg1reduced the decay development by 65 % after 3 weeks[130]
maizeRhizoctonia solaniRsCRZ1reducing lesion areas from 30% to 47%[131]
tomatoBotrytis cinereaBcDCL1/2, BcVDSincreased the protection window 3 weeks on tomato leaves[132]
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Li, M.; Sun, X.; Yin, M.; Shen, J.; Yan, S. Recent Advances in Nanoparticle-Mediated Co-Delivery System: A Promising Strategy in Medical and Agricultural Field. Int. J. Mol. Sci. 2023, 24, 5121. https://doi.org/10.3390/ijms24065121

AMA Style

Li M, Sun X, Yin M, Shen J, Yan S. Recent Advances in Nanoparticle-Mediated Co-Delivery System: A Promising Strategy in Medical and Agricultural Field. International Journal of Molecular Sciences. 2023; 24(6):5121. https://doi.org/10.3390/ijms24065121

Chicago/Turabian Style

Li, Mingshan, Xiaowei Sun, Meizhen Yin, Jie Shen, and Shuo Yan. 2023. "Recent Advances in Nanoparticle-Mediated Co-Delivery System: A Promising Strategy in Medical and Agricultural Field" International Journal of Molecular Sciences 24, no. 6: 5121. https://doi.org/10.3390/ijms24065121

APA Style

Li, M., Sun, X., Yin, M., Shen, J., & Yan, S. (2023). Recent Advances in Nanoparticle-Mediated Co-Delivery System: A Promising Strategy in Medical and Agricultural Field. International Journal of Molecular Sciences, 24(6), 5121. https://doi.org/10.3390/ijms24065121

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