Synthesis And Reasearch Of Reduced Polymer Nanomaterials For Drug Delivery

Polymer nanomaterials can be used as drug carriers by adjusting the composition of polymer and the formation of the state of aggregation conditions.And polymer nanomaterials show the great potential during the controlled release of drugs that can protect the drugs from the external environment before reaching the organization.Disulfide bond in drug-loaded polymers can be restored into mercaptan under high concentration of GSH in cancer cells,generating the site-special release of drugs.In this thesis,we synthesized a series of glutathione-responsive HNTs-polymer nanocomposites and glutathione-responsive core-link micelles having disulfide linkages.Details are as follows:(1)Synthesis of glutathione-responsive HNTs-polymer nanocomposites having disulfide linkagesThe amphiphilic block copolymer MPEG-b-PtBA was successfully synthesized via atom transfer radical polymerization(ATRP).And MPEG-b-PtBA was then dealing with trifluoroacetic acid(TFA),generating the MPEG-PAA with carboxyl groups.Meanwhile,HNTs was functional modification and modified HNTs had amino groups as end groups with disulfide bond.The HNTs-polymer nanocomposites having disulfide linkages was synthesized through the electrostatic attraction of the carboxyl groups in MPEG-PAA and amino groups in modified HNTs.The structure and composition of the copolymer were confirmed by 1H NMR and GPC.The grafting of nanocomposites was investigated by FT-IR,SEM and TG.It is shown that the copolymer was successfully grafted into the modified HNTs.And the gtaft ratio depend on the content of the carboxyl groups in MPEG-PAA.Moreover,the drug release ability was evaluated by encapusing DOX into the HNTs-polymer nanocomposites.In response to GSH as a cellular reducing agnet,the cleavage of disulfide bond in HNTs-polymer nanocomposites caused the cleavage of copolymer from the nanocomposites.Such GSH-triggered cleavage of copolymer led to enhanced release of encapsulated anticancer drugs.Therefore,the GSH-responsive HNTs-polymer nanocomposites offer versatility in multifunctional drug delivery applications.(2)Synthesis of glutathione-responsive core-link micelles having disulfide linkagesThe amphiphilic copolymer MPEG-NSA-Chol was successfully synthesized via free radical polymerization consisting of a hydrophilic PEG chain,a NAS connection chain and a hydrophobic cholesterol chain.The structure and composition of this copolymer was characterized by 1H NMR and GPC.The glutathione-responsive copolymer MPEG-NSAss-Chol was obtained through the linking of cystamine and NSA.FP,DLS,and TEM were employed to study the self-assembly behavior of the products in aqueous solution.It also displayed that the core-link micelles having disulfide linkages had enhanced stability and smaller nano size(10-30 nm).Moreover,it exhibited tunable release of encapsulated drugs,depending on the amount of added thiols(GSH).Thus,there is great potential for this GSH-responsive core-link micelles having disulfide linkages as nanocarriers to form anticancer drugs delivery system.