Study On The Stability Of The Reduction-sensitive Micelles And Applications Of The Copolymer

Stimuli-responsive polymer micelles are promising drug carriers,which can achieve controlled and rapid drug release under stimuli and have better tumor therapeutic effect.Gold nanorods(AuNRs)have unique optical and electronic properties,such as their tunable surface plasmon and high photothermal conversion efficiency.In this thesis,we investigated the effect of modified reduction-responsive polymers on the stability and cytotoxicity of AuNRs.Additionally,the stability and guest molecules exchange behavior of the reduction-sensitive micelles were explored under various conditions.(1).Reduction-sensitive amphiphilic copolymers with a disulfide group were synthesized by a combination of ring-opening polymerization and atom transfer radical polymerization(ATRP).The hydrophobic and hydrophilic segments were biocompatible polycaprolactone(PCL)and polyethylene glycol methyl ether acrylate(POEGA),respectively.In addition,the hydroxyl groups on the hydrophobic chain ends were modified with lipoic acid to obtain LA-PCL-SS-POEGA and the copolymers were characterized by]H-NMR and gel permeation chromatography(GPC).Then AuNRs were modified with LA-PCL-SS-POEGA to replace cetyltrimethylammonium bromide(CTAB).The stability of the modified AuNRs@LA-PCL-SS-POEGA under different conditions was investigated.We further studied the effect of reduction-sensitive polymer on the amount of cellular uptake into Hela cells,and results display that reduction-sensitive polymer enhanced the cellular uptake of the AuNRs.(2).The PCL-SS-POEGA micelles were prepared by precipitation-dialysis method.The stability of reduction-sensitive micelles under various conditions was monitored by fluorescence resonance energy transfer(FRET)method with a FRET pair of DiO and Dil.We first investigated guest exchange behavior of two types dyes DiI and DiO loaded in the reduction-sensitive micelles formed by PCL-SS-POEGA at several pH values with 10 mM DTT or without DTT.The guest exchange rates of PCL-SS-POEGA micelles in the presence of 10 mM DTT at different pH values follows the order:5.5<4.5<6.5<7.5 ? 8.5.However,the results illustrate that the pH value of the solution has a minor influence on the dye exchange rate of reduction-sensitive micelles in the absence of DTT.Then we explored the effect of the content of PCL-SS-POEGA on the guest exchange rate of mixed micelles formed by PCL-SS-POEGA and reduction-insensitive copolymer(PCL-CC-POEGA).Results indicate that the exchange rate and the number of exchanged guest molecules in the micelles increase with the increasing content of reduction-sensitive polymer in the mixed micelles under reducing environment.