Construction Of Three Natural Product Fungicide Delivery Systems And Their Antifungal Activity Against Botrytis Cinerea

Botrytis cinerea,as a kind of airborne plant pathogen,can infect more than 200crop hosts around the world and induce the grey mould disease.The main manifestations of B.cinerea are plant cataplexy,deciduous leaf,flower rot,and soft rot of crop fruits.B.cinerea,as a very common and difficult to control plant fungal disease,can infect crops from seedling stage to maturity stage and cause serious harm to agricultural products and huge economic losses.At present,due to the lack of specific drugs against B.cinerea,the application of chemical synthetic fungicides is still the main strategy for B.cinerea prevention and control.However,the irrational and excessive use of chemical synthetic fungicides can promote the development of resistance in fungal pathogens,and also cause a series of environmental and human health issues.Therefore,it is necessary to adopt a sustainable strategy to control B.cinerea and minimize the adverse effects of fungicides on crops,the ecological environment and human health.In recent years,with the development of nanotechnology,design and preparation of nanoplatforms with controlled drug release capabilities provide many possibilities for the release of pesticides on-demand.Smart stimulus-responsive fungicide nanoplatforms generally use porous nanomaterials as drug carriers,which are combine with fungicide and nanovalve materials through different physical and chemical modification methods to form a nanoplatform that can respond to different external stimuli.The drugs loaded in the nanoplatforms can be released in a controlled manner under different p H,light,temperature,enzyme,and competitor,which can effectively protect crops from plant pathogens and reduce the amount of fungicides.To this end,three eco-friendly fungicide nanoplatforms that can respond to the pathogen microenvironment of B.cinerea are designed and constructed for the prevention and control of B.cinerea.The three nanoplatforms use functionalized mesoporous silica nanoparticles(MSNs)or metal–organic frameworks(MOFs)as carrier materials loaded with botanical fungicides,and then coated with functional nanovalves or polymer materials to form fungicide nanoplatforms.The prepared fungicide nanoplatforms can release the loaded fungicides on demand in the oxalic acid microenvironment created by B.cinerea,and effectively inhibit the growth of B.cinerea,and meanwhile improve the utilization of fungicide and reduce the adverse effects of fungicide on ecological environment and human health.The main contents of this study are as follows:1.Based on the supramolecular chemistry,we design and construct a supramolecular fungicide nanoplatform through a host-guest strategy,which can be responsive to the stimuli of the microenvironment created by B.cinerea.The prepared nanoplatform is based on quaternary ammonium salt(Q)-modified MSNs(MSN-Q NPs)as a carrier,loaded with a botanical fungicide berberine hydrochloride(BH),and carboxylatopillar[5]arene(CP[5]A)as nanovalves to form BH-loaded CP[5]A@MSN-Q NPs for B.cinerea control.In this system,the positively charged Q on the surface of MSN-Q NPs can be encircled with the CP[5]A nanovalve with negatively charged cavity through host-guest interaction to successful block the porous of the nanocarriers and avoid premature release of the fungicides loaded in MSN-Q NPs.In this study,the oxalic acid created by B.cinerea is used as a trigger,so that the prepared fungicide nanoplatform can release the loaded fungicides on demand without using additional stimuli to control the fungicides release.Meanwhile,the prepared fungicide nanoplatform can also reduce the pathogenicity of B.cinerea by reducing the concentration of H~+in oxalic acid microenvironment.In addition,both in vitro and pot experiments show that the prepared fungicide nanoplatform demonstrates excellent antifungal activity by the effective inhibition of mycelium growth and spore germination.Therefore,this microenvironment-stimuli responsive supramolecular fungicide nanoplatform can greatly improve the utilization efficiency of fungicides and reduce the adverse effects of synthetic fungicides on crops and the environment,which opens up a new way for the practical application against B.cinerea.2.Based on the design and research strategy of the previous work,we construct the second nanoplatform for fungicides delivery in response to the microenvironmental stimuli created by B.cinerea.MSNs were used as the nanocarriers,loaded with botanical fungicides eugenol(EU),and then capped with Ag~+-coordinated polydopamine(Ag~+-PDA)as the coating material to form Ag~+-PDA@MSNs-EU NPs.The constructed fungicide nanoplatforms can release the loaded EU and Ag~+in the oxalic acid microenvironment produced by B.cinerea,and up-regulate the expression of plant defense-related genes,realizing the effective prevention and control of B.cinerea.In addition,Ag~+introduced into the system can achieve the synergistic antifungal performance with EU.The in vitro and pot experiments demonstrate that the prepared Ag~+-PDA@MSNs-EU NPs can significantly inhibit the growth of B.cinerea,which is highly feasible for the prevention and control of gray mould disease.3.Based on the disease characteristics of gray mould disease,combined with the host-guest strategy,we design and construct an eco-friendly supramolecular fungicide nanoplatform based on MOFs.This autonomous integrated nanosystem is based on benzimidazole modified MIL-101(Fe)(B-MIL-101(Fe))as nanocarriers,loaded with botanical fungicides osthole(OS),and?-cyclodextrin(?-CD)as nanovalves to form?-CD@B-MIL-101(Fe)-OS supramolecular fungicide delivery nanoplatforms.In this system,?-CD nanovalves with hydrophobic cavity can be encircled with benzimidazole group on the surface of B-MIL-101(Fe)through host-guest interaction to block the porous of MOFs materials and avoid early leakage of the fungicide molecules loaded in the nanocarriers.The prepared nanoplatforms can release the loaded fungicides in the oxalic acid microenvironment produced by B.cinerea,and realize the effective prevention and control of B.cinerea.The experimental results demonstrate that the autonomous integrated supramolecular fungicide nanoplatforms can effectively inhibit the growth of B.cinerea and protect tomatoes from B.cinerea infection at mature stage.This strategy provides a simple and autonomous supramolecular drug delivery system to control B.cinerea and opens up a new way for the development of modern sustainable agriculture.The construction of these three smart response fungicide nanoplatforms that integrate material chemistry,natural product chemistry,polymer chemistry and nanotechnology,will provide new guidance for researchers to design the controlled fungicides release system,which can respond to the microenvironment related to plant pathogens,improve the utilization of fungicide,prevent the spread of diseases in time,and realize the effective control of B.cinerea.