Preparation Of Visible-/nir-light-responsive Surface Molecularly Imprinted Polymers For Application In Photo-controlled Release Of Drug Molecules

Photoresponsive surface molecularly imprinted polymers(PSMIPs)are a new class of functional materials in photoresponsive polymers and are common carriers for drug delivery systems(DDS).They are widely used in food testing,environmental monitoring,drug delivery,and other fields because of their high specific recognition ability,controllable photoresponsive rate,and high stability of target substance binding.PSMIPs mostly require ultraviolet light as a stimuli response condition,moreover,photoresponsive performance in aqueous solutions is poor.These shortcomings limit the application of such smart materials in biological field.In order to meet these challenges,two kinds of azobenzene functional monomers were designed and synthesized.They were prepared on the basis of silica and up-conversion nanoparticles by surface molecular imprinting technique using acyclovir(ACV)and acetaminophen(APAP)as template molecules,respectively.The two polymer materials were applied in visible-/NIR-light-induced release and uptake of ACV and APAP.The dissertation is divided into four parts.The specific content of each chapter is as follows:1.In the first chapter,the research progresses of different classes of stimuli-responsive polymers in drug delivery systems are reviewed.In particular,recent advances in photoresponsive polymers and photoresponsive surface molecularly imprinted polymers have been introduced.In the reported literature,most of the photoresponsive surface molecularly imprinted polymers need to be excited with ultraviolet light.The current research status in visible-light-responsive azobenzene and upconversion luminescent materials for non-UV-induced response are reviewed.The selected topic and significance of the research in this dissertation are proposed,namely the development of non-UV-excited photoresponsive surface molecularly imprinted polymers for photoresponse and photo-controlled drug release in aqueous solution.2.In the second chapter,surface imprinted polymer based on visible-light-responsive azobenzene was prepared and applied to the controlled release and uptake of ACV.A visible-light-responsive surface molecularly imprinted polymer(VSMIP)was prepared by atom transfer radical polymerization(ATRP)using silica spheres,the synthesized visible light-responsive azobenzene N-(4-((4-amino-2,6-dimethoxyphenyl)diazenyl)-3,5-dimethoxyphenyl)methacrylamide(ADDDM),trimethylacryloyloxyethylamine(TEAMA),and ACV as the substrate,functional monomer,crosslinking agent and drug template molecule,respectively.The effects of polymerization conditions,including the ratio of monomer to substrate on the yield and morphology of polymer materials,and the effect of the ratio of monomer and cross-linker on the morphology and photoresponsive performance of the material were investigated.The morphology and chemistry of the material were investigated by SEM,TEM,FT-IR.The adsorption properties of the material were investigated.Visible-light-induced release and uptake of ACV in the solvent and through the skin of chickens,respectively,VSMIP could achieve specific photo-controlled release and uptake of ACV.3.In the third chapter,a drug delivery system for NIR-light-responsive surface molecularly imprinted polymers based on up-conversion materials was prepared and applied to the photo-controlled release and uptake of APAP.Using core-shell structured up-conversion nanoparticles(UCNPs)as a substrate,hydrophilic visible-light-responsive azobenzene 4-((4-(methacryloyloxy)-2,6-dimethylphenyl)diazenyl)-3,5-dimethylbenzenesulfonic acid(MADPADSA)as a functional monomer,and trimethylacryloyloxyethylamine(TEAMA)as a crosslinking agent,and APAP as a drug template molecule,a NIR-light-responsive surface molecularly imprinted polymer(NSMIP)was prepared.The effects of polymerization conditions,including the ratio of monomer to substrate on the yield and morphology of polymer materials,the effects of the ratio of monomer to crosslinker on the morphology and photoresponsive performance of the materials,and the intensity of up-conversion fluorescence emission were investigated.The impact of the material morphology,chemical structure and up-conversion fluorescence luminescence properties were characterized.The material adsorption properties were studied.Photo-controlled release and uptake of APAP in solvents was performed.NSMIP could achieve specific photo-controlled release and uptake of APAP.NIR-light-induced APAP release in the solvent and through the pork tissue,respectively,NSMIP could achieve specific photo-controlled continuous release of APAP.4.The fourth chapter summarized the research work and experimental results.This dissertation designed and synthesized two visible light response azobenzene ADDDM and MADPADSA,and optimized the synthesis route.Then,visible-/NIR-light-responsive surface molecularly imprinted polymers were prepared and characterized,respectively,based on silica,upconversion nanoparticles.The two molecularly imprinted polymer materials have excellent specific adsorption capacities for acyclovir and acetaminophen,respectively.Finally,both molecularly imprinted polymer materials were successfully delivered through the biological tissue for photo-controlled drug release.Based on this paper,the future research work was prospected,and the direction of further optimization research was clarified.