Synthesis And Self-assembly Of Block Polymer With Disulfide Bonds

With the development of polymer chemistry,polymer colloidal particles with different structures and various functional groups have been synthesized,andhave found applications in many fields such as ion detecting,cargo delivery and imprinting.In these years,in order to find applications in medical and biological science many different functional groups,such as disulfides and thiols,have been introduced into polymer colloidal particles.Disulfide bonds,which are formed under oxidation conditionby two thiol groups,can be reduced into thiol groups by reductants under mild conditions.The exchange reaction between thiol groups and disulfide bond make the colloid particles redox-responsiveness.In this thesis,we make use of different types of controlled radical polymerizations including reversible addition-fragmentation chain transfer(RAFT)polymerization and atom transfer radical polymerization(ATRP)to synthesize polymers of different structures with disulfide bonds.These polymers were subsequently self-assembled into micelles in solutions.The crosslinked polymeric micelles can be dissociated upon cleavage of the disulfide bonds.1.Synthesis of diblock copolymers containing disulfide bonds at the junction pointsDiblock copolymers containing disulfide bondshave been synthesized by using the method of RAFT polymerization transfer ATRP.First,RAFT polymerization ofstyrene was employed to preparepolystyrene marco RAFT agent(PS-RAFT).The terminal RAFT agents of PS were reduced to sulfhydryl groups(PS-SH)in the presence of primary amine,and the ATRP macroinitiator(PS-S-S-Br)was prepared by an exchange reaction between PS-SH and an ATRP initiator containing disulfide bonds.Then,PS-S-S-Br was used to initiate the polymerization of 2-hydroxyethyl methacrylate(HEMA)and PS-S-S-PHEMA diblock copolymers with disulfides at the junction points were obtained.Kinetics study of ATRP of HEMA shows the characteristic of living polymerization.In methanol,the diblock copolymer self-assembles into polymeric micelle with PS cores and PHEMA coronae.Transmission electron microscopy and dynamic light scattering were used to study the morphology changes of the micelles after cleavage of the disulfide bonds.The result shows a new methd to prepare block copolymers with disulfide bonds at the junction points.2.Preparation of temperature-sensitive polymer micelle by protein crosslinkingAn environmental-responsive micelle with protein components and disulfide crosslinks was prepared.RAFT polymerization of di(ethyleneglycol)methyl ether methacrylate was employed to prepare marco RAFT agent(PDEGMA-RAFT).Then the PDEGMA-RAFT was used to prepare a diblock copolymer by RAFT polymerization of Poly(ethylene glycol)methyl ether methacrylate(Mn: 500)and pyridyldisulfide ethyl methacrylamide(PDSMA).The prepared diblock copolymer PDEGMA-b-P(PEGMA500-co-PDSMA)exhibits lowest critical solution temperature(LCST)near the human body temperature.At a temperature above the LCST in water,the copolymer and can self-assemble into temperature-sensitive micelles with PDEGMA as the core and P(PEGMA500-co-PDSMA)as the shell.Bovine Serum Albumin(BSA)was reduced to produce multi-thiol groups and was used to crosslink the shell of the micelle through exchange reactions with the pyridyl disulfide groups in PDSMA.As the temperature was lowered to below the LCST,the PDEGMA chains in the core were dissolved,driving the micelles to swell.Therefore,we built a bionic micelles of environmental response type based on protein disulfide bond crosslinking.