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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

Smart controlled-release avermectin nanopesticides based on metal–organic frameworks with large pores for enhanced insecticidal efficacy

Jincan Liu,Dejin Xu,Guangchun Xu,Xiaona Li,Jiangtao Dong,Xingkun Luan,Xuezhong Du

Nanopestcides based on metal–organic frameworks (MOFs) have attracted great attention. Highly stable mesoporous metal–organic framework PCN-777 with large pores can accommodate the biologically active insecticide avermectin (AVM) of relatively large molecular dimensions. In this work, PCN-777 nanoparticles were synthesized for the creation of double-gated nanopesticides with sodium lignosulfonate (SL) and chitosan. The double gatekeepers could realize excellent sealing performance to prevent premature leakage of AVM. The double-gated PCN-777 based nanopesticides could achieve the controlled release of AVM in response to pH, laccase, phosphate, and phytic acid (PA), which are related to the physiological environments of pests and crops. The PA-triggered controlled release of loaded cargos in MOF-based delivery systems was reported for the first time. This is the first example of PCN-777 drug/pesticide delivery system and also the first case of controlled-release MOF-based AVM nanopesticides, and the mechanisms of the stimuli-responsive controlled pesticide release were clearly elucidated. The nanopesticides prevented the ultraviolet photolysis of AVM owing to the PCN-777 organic ligands and SL coating. The nanopesticides had high insecticidal efficacy and field control efficacy against the pests Spodoptera litura Fabricius on cabbage, in comparison with traditional pesticide formulations, and the nanopesticides had no influence on plant growth and showed high biosafety toward non-target organisms and human cells. The smart controlled-release nanopesticides show high potential and application prospect in ecological agriculture.

研究领域: 农业科学 · 生物技术 · 环境科学
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GREEN CHEMISTRY · 2022 ·Vol. 24 ·期 9 ·3667-3676 · IF 11.034

A design approach to eliminate the toxic effect of insecticides to ensure human safety

Bin He,Pengbing Chang,Sufeng Zhang,Xing Zhu

Encapsulating toxic insecticides in a system to reduce their impact on non-target organisms and the environment, thereby enhancing pest control specificity and ensuring human safety, is important but there exist numerous challenges. In the present study, a cellulase-responsive carrier for the controlled release of avermectin (AVM) was prepared based on poly (ethylene glycol) diacrylate (PEGDA)-anchored porous regenerated cellulose microspheres (RCMs), with the goal of realizing their application as insecticide carriers for enzyme-mediated controlled release. Since the as-prepared RCMs showed an excellent loading ability for AVM, biocompatible PEGDA was used to block cellulose micropores and prevent the leakage of AVM. Thus, human safety was ensured. The results show that the cell viability was maintained at 90% in the AVM-loaded microspheres group after 5 days while it was only 70% in the free AVM group, indicating that the system is considerably safer for the human body. Furthermore, the AVM-loaded microspheres group showed excellent toxicological properties against Plutella xylostella and mole cricket. The lethality rates against the two target insects were 90 and 82%, respectively, at a concentration of 60 mg L−1, indicating the high efficacy of the insecticide. This work provides a feasible strategy to eliminate the toxic side effects of insecticides, which is of great significance to agricultural safety.

研究领域: 农业科学 · 生物材料学 · 环境科学
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ACS Catalysis · 2025 · IF 13.1

Cytochrome P450-Catalyzed Tetrahydrofuran Formation via Dual Pathways in Avermectin Biosynthesis

Tianjian Sun,Mingyu Liu,Shuai Li,Jiawei Guo,Lei Liu,Lixin Zhang,Li Ma,Shengying Li

Avermectins (AVMs) are a class of 16-membered ring macrolides produced by Streptomyces avermitilis. Renowned for their potent insecticidal and acaricidal properties, AVMs are widely used as environmentally friendly biopesticides. Although the biosynthetic gene aveE encoding a cytochrome P450 monooxygenase was identified 30 years ago, its exact catalytic function and mechanism have remained elusive due to a lack of biochemical characterization. Here, we overcome the long-standing challenge in soluble and functional protein expression of AveE in Escherichia coli and reconstitute the in vitro activity of this P450 enzyme using surrogate redox partner proteins. Time-course studies reveal monohydroxylation at the C8a position of the substrates as the initial step, subsequently leading to tetrahydrofuran (THF) ring formation. Isotopic labeling experiments provide significant insight into the catalytic mechanism of AveE, revealing the cooperation of the C8a,C6-diol pathway and the C6-nucleophilic attack pathway. This study not only presents an effective strategy for heterologous expression of difficult P450 enzymes in E. coli but also elucidates the exact process of THF ring formation during AVM biosynthesis.

研究领域: 微生物学 · 酶学 · 生物化学
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Materials Science & Engineering C-Materials for Biological Applications · 2019 · IF 4.959

Coordination bonding-based polydopamine-modified mesoporous silica for sustained avermectin release

Zhichuan Shen,Hongjian Wen,Hongjun Zhou,Li Hao,Huayao Chen,Xinhua Zhou

Mesoporous silica nanoparticle (MSN) is a novel vehicle to deliver pesticide. MSN can be modified with different chemical groups to increase its interaction with pesticides. In this study, polydopamine-modified mesoporous silica (MSN-PDA) was prepared through a one-pot method with the addition of dopamine (DA). Copper ions, zinc ions, and iron ions were impregnated on MSN-PDA. In addition, avermectin (AVM) was used as the model drug. We investigated the materials' structure, adsorption and release behaviors, anti-UV properties, as well as their adhesive capability, especially the bridge effect of metal ions, π-π stacking of PDA and electrostatic interaction. The results demonstrated that the above materials possessed spherical morphology with surface areas from 635.833 to 1048.960 m 2 /g. Except for the zinc ions, the complexation with copper and iron ions not only enhanced materials' UV resistance but also increased their adsorption rate and the loading amount of AVM from 133 mg/g to 248 and 243 mg/g, respectively. At pH 3, 7, and 10, the bridge effect of the metal ions demonstrated a cumulative release rate using MSN-PDA not over 30% for AVM in 180 h, while the cumulative release rate for MSN reached its 50% in 60, 90, and 50 h under different pH values, respectively. We further demonstrated that the adhesive effect of PDA could be decreased by metal ions.

CAS / MDL: 62-31-7 57-09-0 78-10-4
研究领域: 材料科学 · 化学 · 农药递送系统
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JOURNAL OF POLYMERS AND THE ENVIRONMENT · 2018 ·Vol. 26 ·期 7 ·2945-2953 · IF 1.971

Preparation of Avermectin/Grafted CMC Nanoparticles and Their Sustained Release Performance

Chen Huayao,Lin Guanquan,Zhou Hongjun,Zhou Xinhua,Xu Hua,Huang Suqing

Avermectin (AVM) is a highly efficient pesticide against a variety of insects and is widely used in agriculture. However, it is susceptible to oxidation and photolysis, resulting in instability under UV irradiation and a short half-life. Herein, sodium carboxymethyl cellulose (CMC) was grafted by styrene (St), Methyl methacrylate (MMA) and butyl acrylate (BA) respectively to prepare grafted polymer nanoparticles in application for AVM sustained released. And the influence of different grafted monomer and the grafted rate on the AVM/grafted polymer nanoparticles performance was discussed. The larger the grafted rate of St was, the larger the particle size of AVM/grafted polymer nanoparticles had with a higher drug loading rate and stronger resistance to ultraviolet light. Besides, the particle size, drug loading rate and the ability of anti-ultraviolet light of grafted CMC emulsion was also influenced by the modifying agent. While the concentration of AVM was kept the same, the acrylic esters (MMA and BA) grafted emulsion have smaller particle sizes with higher drug loading rates and stronger anti-ultraviolet ability comparing to styrene (St) grafted emulsion. The effect of different amount of St and different monomer grafted on the sustained release performance of AVM/grafted polymer was also investigated. As the grafted rate of St increased, the release rate became smaller. The release speed has a sequence of CMC-g-PBA > CMC-g-PS > CMC-g-PMMA when CMC grafted with different monomer. Their sustained release curves can be described by Korsmeyer-Peppas equation. Finally, the insect toxicity test showed that insecticide toxicity against diamondback moth ( Plutella xylostella L.) has no apparent difference among the AVM and AVM/grafted polymer nanoparticles indicating that AVM/grafted polymer nanoparticles can reduce the amount of organic solution used for dissolution and prolonged its service life without decreasing its insecticide toxicity.

CAS / MDL: 9004-32-4
研究领域: 农业科学 · 材料科学 · 农药学
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ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH · 2019 ·Vol. 26 ·期 24 ·25107-25116 · IF 2.914

Enzyme and pH dual-responsive avermectin nano-microcapsules for improving its efficacy

Liu Guanghua,Lin Guanquan,Lin Xida,Zhou Hongjun,Chen Huayao,Hao Li,Zhou Xinhua

The overdosage use of pesticide was harmful to the environment and human health, which was mainly caused by the low utilization rate of the pesticide. However, the pesticide microcapsule with sustained-release and stimulating response properties could effectively solve this problem. Preparation of carboxymethyl cellulose grafting dimethyldiallylammonium chloride (CMC-g-PDMDAAC) through grafting polymerization and trapping as well as encapsulation of avermectin (AVM) via electrostatic interactions resulted in the formation of AVM/CMC-g-PDMDAAC microcapsules. The results showed that the particle size was 200~300 nm. The encapsulation efficiency was as high as 72.06%. Furthermore, the remaining rate of encapsulated AVM increased from 50.0 to 81.60% after UV irradiation for 359 min. The microcapsules exhibited significant enzyme and pH stimuli responsiveness. Finally, CMC-g-PDMDAAC had no significant difference effect on the toxicity of AVM, AVM could be found, and DMDAAC featured a synergistic effect on the toxicological effects of AVM. Graphical abstract

CAS / MDL: 9004-32-4
研究领域: 农药科学 · 材料科学 · 环境科学
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FISH PHYSIOLOGY AND BIOCHEMISTRY · 2023 · IF 2.9

Mitigation of avermectin exposure-induced brain tissue damage in carp by quercetin

Xu Xuhui,Zhou Mengyuan,Xie Kunmei,Zhang Shuai,Ji Xiaomeng,Sun Ying,Li Qiulu,Dong Zibo

Avermectin is widely used as an important insecticide in agricultural production, but it also shows strong toxicity to non-target organisms. Quercetin is a natural flavonoid that is widely used due to its good anti-inflammatory and antioxidant effects. We believe that quercetin may have a potential therapeutic effect on avermectin poisoning. This experiment was proposed to observe the effect of quercetin on the toxic response to avermectin by observing the toxic response caused by avermectin in the brain of carp. In this project, 60 carp were studied as control group (Control), quercetin administration group (QUE), avermectin exposure group (AVM) and quercetin treatment avermectin exposure group (QUE + AVM) with different interventions to study the effect of quercetin on avermectin. The carp brain tissues were stained and simultaneously analyzed for blood–brain barrier (BBB), oxidative stress indicators, inflammatory factors, and apoptosis using qPCR technique. The results of the study indicate that avermectin exhibits a neurotoxic mechanism of action in fish by decreasing the transcript levels of tight junction protein-related genes, which in turn leads to the rupture of the BBB in the carp brain tissue. Avermectin induced apoptosis in carp brain tissue by increasing oxidative stress response and promoting inflammatory cell infiltration. Quercetin could reduce the accumulation of reactive oxygen species (ROS) in the brain tissue of carp caused by avermectin exposure toxicity, maintain redox homeostasis, reduce inflammatory response, and protect brain tissue cells from apoptosis. The present study confirmed the therapeutic and protective effects of quercetin on neurotoxicity in carp caused by avermectin exposure.

CAS / MDL: 117-39-5 65195-55-3
研究领域: 水产毒理学 · 环境科学 · 药理学
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ACS Agricultural Science & Technology · 2024 · IF 2.3

Self-Assembly Mechanism of Avermectin B1a and Its Activity against Potato Rot Nematode

Weibing Xu,Shengjing Chu,Fei Pan,Rourou Wang,Haitao Long,Lumei Pu,Huixia Li

Many of the carriers used in the delivery of avermectin (Avm) B1a, a widely used crop pesticide, may lead to environmental safety problems. Here, we tested the self-assembly of Avm B1a without an exogenous excipient for improved environmental safety and drug activity. Our results showed that various solvents, including ethanol, methanol, acetone, dimethyl sulfoxide, and N,N-dimethylformamide, can be used to prepare Avm B1a self-assembled nanoparticles. Nuclear magnetic titration experiments revealed that the intermolecular hydrogen bond was the main binding force in Avm B1a self-assembly. Molecular dynamics simulations indicated that the number of hydrogen bonds increased to 10 and 20 in the assembly system of 16 and 32 Avm B1a molecules, respectively, over a period of 500 ns. The assembled Avm B1a presented a structured spherical shape, and particle size could be effectively regulated with the initial concentration. The permeability in soil and anti-UV degradation capacity were, respectively, 3.5 and 2.0 times higher for self-assembled nanoparticles with a size of 128 nm than for pure Avm B1a. The activity of nanoparticles against potato putrid stem nematode was higher than that of pure Avm B1a; in that, particles with a size of 128 nm exhibited the highest activity, and the 24 h and 48 h activity was, respectively, 16 and 20% higher than that of pure Avm B1a. In vivo fluorescence experiments showed that the fluorescence in nematodes increased with the increase in chemical concentration and time.

CAS / MDL: 81-88-9
研究领域: 药学 · 纳米技术 · 农药化学 · 环境科学 · 植物病理学
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EUROPEAN POLYMER JOURNAL · 2024 · IF 5.8

ROS sensitive micelles of carbon dioxide based amphiphilic polymer for delivery of avermectin

Qingshaung Qiu,Yanli Zhao,Yongsheng Niu,Hongchun Li

A novel amphiphilic polymer, methoxy polyethylene glycols (mPEG)-3, 3′-(propane-2, 2-diylbis (sulfanediyl)) dipropionic acid (TK)-poly (propylene oxide-co-carbon dioxide-co-allyl glycidyl ether) (PPAG) (mPEG 2000 -TK-PPAG), was successfully synthesized for delivery of avermectin (AVE). The chemical structure was characterized by FTIR. In aqueous medium, mPEG 2000 -TK-PPAG could self-assembled into micelles. The AVE loaded mPEG 2000 -TK-PPAG micelles showed a considerable drug-loading content of 19 %. The prepared micelles were spherical morphology with average hydrodynamic diameter 469.4 nm and zeta potential of around –33.6 mv. AVE was released slowly from the AVE loaded mPEG 2000 -TK-PPAG micelles in a neutral condition and was released rapidly under stimulation of reactive oxygen species (ROS). Therefore, this ROS responsive micelle formulation achieves target control of pests and provides an efficient micelle platform for green agriculture.

CAS / MDL: 538-75-0 1122-58-3
研究领域: 农业科学 · 材料科学 · 药剂学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2017 · IF 3.154

Fabrication of Novel Avermectin Nanoemulsion Using a Polyurethane Emulsifier with Cleavable Disulfide Bonds

Wenxun Guan,Wenxiang Zhang,Liming Tang,Yan Wang,Haixin Cui

In this study, a polyurethane emulsifer with various functional groups was prepared from isophorone diisocyanate, avermectin, 2,2-dimethylol propionic acid, and bis(2-hydroxyethyl) disulfide. The chemical structure of the polymer was confirmed by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance, and element analysis. The polymer exhibited adequate emulsification ability for avermectin after neutralization with triethylamine. A satisfaying nanoemulsion was obtained, in which avermectin was encapsulated in nanoparticles with 50 wt % drug loading, low organic solvent content, and high stability under dilution and centrifuging treatment in addition to low surface tension, high affinity to crop leaf, and improved avermectin photostability. The resulting nanoparticles showed degradability in the presence of dl-dithiothreitol or inside the insect as a result of the disulfide bonds, promoting the release of avermectin. As a result, the avermectin nanoparticles showed higher insecticidal ability compared to both the avermectin nanoparticles without a disulfide group and the avermectin emulsifiable concentrate.

研究领域: 纳米技术 · 药学 · 农药化学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2019 · IF 3.973

Enzyme cum pH dual-responsive controlled release of avermectin from functional polydopamine microcapsules

Hongjian Wen,Hongjun Zhou,Li Hao,Huayao Chen,Hua Xu,Xinhua Zhou

Novel enzyme cum pH dual-responsive microcapsule were prepared with an aim to enhance the utilization of pesticides and reduce environmental pollution. The synthetic procedure involved the introduction of urea bonds by forming a covalent bond between isocyanate–functionalized polydopamine (PDA) microcapsules and polyethyleneimine (PEI). The prepared AVM@PDA-IPTS-PEI microcapsules could effectively protect avermectin (AVM) from ultraviolet radiation, and thus decelerate the decomposition rate; the cumulative release showed positive correlations with pH and the urease activity. The AVM release rate was highest at pH 10. At pH 7, the release rate was enhanced after addition of urease, showing improved urease-responsive property under neutral or weak base condition. Especially at pH 7 in presence of urease, the release behavior was in agreement with the Logistic model and able to describe the S-shaped/sigmoidal release profiles, whereas Korsmeyer–Peppas model was better suited in the absence of urease, as the value of K 1 was smaller than 0.45, suggesting that the behavior was controlled by Fick’s diffusion. AVM@PDA-IPTS-PEI displayed better adhesion property than AVM, and the microcapsule ameliorated foliage wettability. AVM@PDA-IPTS-PEI exhibited the insecticidal property similarly with AVM, which can be used for reducing the applied quantity of pesticides and improving their efficacy.

研究领域: 农业科学 · 材料科学 · 环境科学
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Royal Society Open Science · 2019 ·Vol. 6 ·期 7 · IF 2.515

Soy protein isolate-carboxymethyl cellulose conjugates with pH sensitivity for sustained avermectin release

Long Chen,Hongjun Zhou,Li Hao,Huayao Chen,Xinhua Zhou

Carboxymethyl cellulose (CMC) was grafted onto the surface of soy protein isolate (SPI) to obtain soy protein isolate-carboxymethyl cellulose conjugate (SPC). Avermectin (AVM) was hydrophobically encapsulated as a model drug to obtain SPC@AVM. The reaction between SPI and CMC was confirmed by infrared spectroscopy, thermal analysis and SDS-PAGE electrophoresis. The results of scanning electron microscopy showed that the average particle size of the drug-loaded microspheres was 129 nm and the shape of microspheres changed from block to spherical after the addition of AVM. After encapsulation of AVM, the absolute value of zeta potential was greater than 15 mV, which indicated better stability. Compared to AVM solution, SPC@AVM showed more wettability on the leaf surface and the contact angle on the leaves decreased from 71.64° to 57.33°. The maximum liquid holding capacity increased by 41.41%, from 8.85 to 12.52 mg cm−2, which effectively reduced leaf loss. SPC@AVM also prevented UV photolysis, wherein the half-life was extended from 18 to 68 min when exposed to UV light. Moreover, toxicity tests showed that the encapsulation of AVM was beneficial to retain the insecticidal effect of AVM in the presence of ultraviolet light. The release rate of AVM showed pH responsiveness and the release rate under neutral conditions was faster than acidic and alkaline conditions. Moreover, the process conformed to the Weibull model.

研究领域: 材料科学 · 药学 · 农业科学
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