Preparation Of PH-responsive Polymers By Thiol-ene Click Reaction

Nowadays,human life and health have been seriously threatened by cancer.Generally speaking,the treatment of cancer include operative therapy,chemotherapy,radiotherapy and diet therapy.However,there are some shortcomings in the above traditional cancer treatment methods.The traditional antitumor drug delivery systems which deliver small molecule anticancer drugs,damage normal cells seriously and make side effects.However,intelligent drug delivery systems have little toxicity and side effect,good biocompatibility,long residence time and large loading capacity etc.Therefore,the intelligent macromolecular materials show great application prospect in anticancer drugs transportation systems.Biodegradable polymer micelles have emerged as one of the most promising anticancer drugs delivery nanosystems for the target control and delivery of antitumor drugs.The amphiphilic triblock polymers are capable of self-assembly to form polymeric micelles in aqueous.The hydrophobic block shrinks inward,and the hydrophilic part extend outward,forming polymeric nanoparticles with core-shell structure.In order to increase the release of antitumor drugs in cancer cells,different pH-responsive micelles have been developed based on acid-labile bonds,such as hydrazone bond,acetal bond,?-thiopropionate,etc.Based on a large number of literature research,three kinds of amphiphilic triblock copolymers were synthesized via a simple thiol-ene click chemistry reaction.Two of them were the polymers with ketal structure,another was the polymer that contents ketal structure and ?-thiopropionate structure.The structures of the polymers were characterized by 1H NMR and gel permeation chromatography(GPC).Nile red was used as fluorescence probe to determine the critical micelle concentration(CMC)of polymeric micelles.The results showed that the critical micelle concentration(CMC)of polymeric micelles decreased with the increase of hydrophobic chain length.In addition,the particle sizes and morphologies of the polymeric micelles were characterized by dynamic light scattering(DLS)and transmission electron microscopy(TEM).The pH-responsiveness of polymer micelles were studied by using Nile Red fluorescence.The results demonstrated that hydrophobic Nile Red could be loaded in the micelles that were stable at pH=7.4.Polymeric micelles prepared from Pb were stable at pH=7.4,but the Nile red was released slowly in the acid environment of pH=5.pH-dependent destabilization of polymeric micelles was studied by dynamic light scattering(DLS).The result that the micellar particle size expanded from 144 nm to 255 nm,and finally reduced to 55 nm,was due to the hydrolysis of ?-thiopropionate structure,leading to fracture the backbone of polymer micelles.Polymer micelles were stable in neutral environment,but in acidic environment Nile red was released slowly due to the destruction of polymer micelle structure due to the hydrolysis of ?-thiopropionate.Therefore,the pH-responsive amphiphilic triblock copolymer is a promising drug delivery material,which can be used in the transport and release of hydrophobic anticancer drugs.