Micro Environmental Stimuli-responsive Polymer Used As Drug Carrier Synthesized By RAFT Polymerization

Using the characteristic of tumour tissue extracellular environment(comparing with the normal tissue,it has an over expressing of substance such as glutathione and cathepsin B,a lower pH value and higher temperature),we synthesized several kinds of RAFT(Reversible addition-fragmentation chain transfer)agents.Therewith we synthesized stimuli-responsive block copolymers by using these kinds of RAFT agents.These block copolymers have the potential to be used as drug carriers.Glutathione is a kind of reductive short peptide which can react with oxidative substance.Cathepsin B is a kind of proteolytic enzyme which can recognize and cleave some peptide with particular sequence.By taking advantage of the characteristics of these substances,relevant RAFT agents and polymers were synthesized.First,two kinds of difunctional RAFT agents were synthesized by organic synthesis,and purified by silica gel column chromatography.These RAFT agents include oxidative disulphide bond.Then two kinds of monomers,2-(dimethylamino)ethyl methacrylate(DMAEMA)and N-Isopropyl acrylamide(NIPAM),were polymerized into block copolymers by RAFT polymerization.The ends of these block copolymers are the RAFT functional group.By aminolysis and oxidation coupling,the redox-responsive multi-block copolymers were synthesized.The NMR and GPC were used to characterize the polymers.By using the solid-phase synthesis,peptide-RAFT agent conjugate was synthesized.The product was purified by the HPLC,and characterized by NMR,ESI-MS and HPLC.The peptide-RAFT agent conjugate include a peptide of GLFG sequence which could be cleaved by the cathepsin B.Then a macro RAFT agent was obtained by connecting the peptide-RAFT agent conjugate and methoxy polyethylene glycol.A kind of block copolymer was synthesized by using DMAEMA as the monomer and macro RAFT agent as the chain transfer agent.The resulting block copolymer was investigated by NMR and GPC.