Study On Linear-dendritic Block Copolymers Based On Poly(Hydroxyethyl Glutamine) And Poly(Vinyl Lactam)

The enzyme-responsive polymers have great potential in applications of biomedical field such as drug delivery,disease diagnosis and biotechnology due to their good biocompatibility and high selectivity.Linear-dendritic block copolymers(LDBCs)consist of covalently bound linear polymeric chains with the regular and well-defined dendritic segments,which are particularly attractive due to their multicomponent constitutions,unique self-assembly properties,and multivalent characteristics.So far,there have been a number of reports on amphiphilic enzyme responsivelinear-linearblockcopolymers.However,enzymeresponsive linear-dendritic block copolymers(LDBCs)have seen only limited exploration.In this thesis,two novel series of enzyme-responsive amphiphilic linear-dendritic block copolymers(LDBCs)were designed and synthesized,and their self-assembly behavior in aqueous solution and the enzyme-responsive performance were also studied.The well-defined amphiphilic linear-dendritic diblock copolymers(G-b-PHEG and PHEG-G_n-bis-MPA(n=1,2))based on hydrophilic linear block of poly(hydroxyethyl L-glutamine)(PHEG)and a hydrophobic dendron derived from cysteamine or aliphatic polyester of 2,2'-dimethylolpropionic acid(bis-MPA)have been synthesized via a“dendron-first”strategy.The structure of copolymers was characterized by ~1HNMR,IR and GPC.Their self-assembly behavior in aqueous solution and the enzyme-responsive performance were investigated via fluorescent spectrometer,TEM and~1HNMR spectra.The results showed that G-b-PHEG and PHEG-G_n-bis-MPA can self-assemble into micelles in water.The micelles encapsulate fluorescent dye Nile red.After papain stock solution was added to the micellar aqueous solution,the dye molecules were released into the aqueous environment upon the disassembly of the micelles and their fluorescence intensity decrease,lead to the solutions become turbid and precipitates.The disassembly of the micelles was depended on the concentration of papain and the generation of dendrons in LDBCs.The higher the enzyme concentration is,the faster disassembly rate is.And the higher of the generation,the slower of the disassembly rate.The results suggested that these block copolymers the micelles have a desired enzyme-responsive disassemble behavior.The first-andsecond-generation amphiphilic linear-dendritic diblock copolymers(PNVP-G_n-bis-MPA(n=1,2)and PNVCL-G_n-bis-MPA(n=1,2))based onhydrophiliclinearblockofpoly(N-vinylpyrrolidone)(PNVP)or poly(N-vinylcaprolactam)(PNVCL)and aliphatic polyester dendrons as a hydrophobic block were synthesized via a“chain-first”strategy.The structure of copolymers was characterized by~1HNMR,IR and GPC.The results showed that PNVP-G_n-bis-MPA and PNVCL-G_n-bis-MPA can self-assemble into micellar aggregates,which can also disassemble after the papain was added.The disassembly rates of the aggregates were depended on the generation of dendrons in LDBCs.The higherthegenerationis,theslowerthedisassemblyrateis.The thermal-responsiveness of PNVCL-G_n-bis-MPA was also studied,the results presented that the thermal-responsiveness of the copolymers were depended on their concentrations and generation.The LCST values of the copolymers decrease with increasingtheirgenerationandconcentrations.Thus,thecopolymers PNVCL-G_n-bis-MPA display enzyme and thermal responsive properties.