Study On PH,Temperature And Enzyme Responsive Linear-dendritic Block Copolymers Using Poly(Hydroxyethyl Methacrylate) As A Linear Chain

Multiple stimuli-responsive amphiphilic linear-dendritic block copolymers(LDBCs)micelles can respond to a variety of environmental changes and enhance the versatility of smart materials,which can meet multiple needs in practical applications.They have potential applications in drugs and gene carriers,biomimetic materials,sensors,and special separation systems.Compared with linear-linear block polymers,LDBCs have higher drug loading capacity,stability,and more adjustable physical and chemical properties.However,at present,the literatures on multiple stimuli-responsive polymers are mostly linear-linear block polymers,while the research on linear-dendritic block copolymers(LDBCs)has rarely been reported.In this thesis,we have synthesized amphiphilic linear-dendritic block copolymers PDHEMA-b-Gly-Phe-G_n(n=1-3)base on hydrophilic linear partially ketal-protected poly(hydroxyethyl methacrylate)(PDHEMA)and hydrophobic dendritic polyethers linked by a glycyl-phenylalanine dipeptide.The copolymers were prepared by atom transfer radical polymerization(ATRP)and alkynyl/azide(CuAAC)"click"reaction.Their structure was characterized by ~1 H NMR,FT-IR,ESI-MS and GPC.Their self-assembly behavior and stimuli-responsive properties were investigated by ~1 H NMR spectra,fluorescence spectra,TEM,UV spectra and particle size analyzer.The results showed that the second and third generation copolymers PDHEMA-b-Gly-Phe-G_n(n=2,3)can self-assemble to form nanospherical micelles in aqueous solution.The self-assembled micelles show pH,thermal and enzymatic responsiveness,which can disassemble and release the encapsulated hydrophobic dye Nile red or anticancer drug paclitaxel when the pH changes from 7.4 to 5.5,the temperature changes from 37°C to 42°C,or/and upon the addition of?-chymotrypsin.In addition,the disassembly and release rates depended on the generation of dendrons in LDBCs.The higher the generation of dendrons in LDBCs is,the slower the disassembly rate for enzyme-responsive behavior,the faster the disassembly rate for thermal-responsive behavior.The results of drug loading and in vitro drug release experiments showed that the maximum drug loading ratios of PDHEMA-b-Gly-Phe-G_n(n=2,3)to paclitaxel were determined to 1:4 and 1:3(mass ratio of paclitaxel to copolymers),the maximum drug loadings are 17.13%and 21.97%,and the corresponding encapsulation rates are 85.65%and 87.88%,respectively.Compared to single stimulus,the release rate and the cumulative release of paclitaxel from the micelles increased when stimulated by double and triple stimulus.The cumulative release amount reached the highest with thermal and enzymatic double stimulus.Thus,PDHEMA-b-Gly-Phe-G_n(n=2,3)micelles are responsive to pH,and thermal and enzymatic triple stimulus.The results of this thesis provide experimental basis for the research and development of new targeted drug carriers.