Study On PH And Enzyme Dual-Stimuli Responsive Linear-Dendritic Block Copolymers Using Poly （N,N-Dimethylaminoethyl Methacrylate） As A Linear Chain

Multi stimulus responsive amphiphilic linear-dendritic block copolymers（LDBCs）have broad application prospects in intelligent drug delivery systems.Poly（N,N-dimethylaminoethyl methacrylate）（PDMAEMA）is a pH,thermal and CO₂response polymer,and phenylalanyl-lysine（Phe-Lys）dipeptide can be cleaved by trypsin or cathepsin B.The combination of PDMAEMA and Phe-Lys dipeptide into LDBCs molecules is expected to obtain copolymers with multiple stimulus responsiveness.However,the studies on the LDBCs with PDMAEMA as a linear chain are rarely reported.In this thesis,the atom transfer radical（ATRP）polymerization of N,N-dimethylaminoethyl methacrylate（DMAEMA）was firstly studied with ethyl2-bromoisobutyrate as an initiator and Cu Br as a catalyst.The effects of two ligands N,N,N’,N”,N”-pentamethyldiethylenetriamine（PMDETA）and 2,2’-bipyridine（bpy）,bulk and solution polymerization on the polymerization were investigated.PDMAEMA with narrow molecular weight distribution was obtained.Two amphiphilic linear-dendritic block copolymers PDMAEMA-b-dendr（Phe-Lys）_n（n=1,2）with PDMAEMA as a linear chain and Phe-Lys dipeptide as dendrons were prepared by bstepwise condensation polypeptides synthesis method.Their structures and molecular weight were characterized by ~1H NMR spectra and GPC.The self-assembly behavior and stimulus response properties of the copolymers in aqueous solution were studied by ~1H NMR spectra,fluorescence spectroscopy,transmission electron microscopy（TEM）and particle size analyzer.The results showed that PDMAEMA-b-dendr（Phe-Lys）_n（n=1,2）can self-assemble into spherical micelles in aqueous solution.The second-generation copolymer PDMAEMA-b-dendr（Phe-Lys）₂ formed more stable micelles than the first-generation copolymer PDMAEMA-b-dendr（Phe-Lys）₁.The copolymer micelles can encapsulate the hydrophobic dye Nile red or the anticancer drug doxorubicin（DOX）.In a buffer solution of pH 5.5 or after adding trypsin,the copolymer micelles disassemble and release the encapsulated small molecules.Compared to single stimulation（just under mildly acidic conditions or with the addition of trypsin）,the disassembly rate of copolymer micelles to release the encapsulated drug doxorubicin under dual stimulation in pH 5.5 buffer solution with the addition of trypsin is faster,indicating that the synthesized PDMAEMA-b-dendr（Phe-Lys）_n（n=1,2）are enzyme and pH dual-stimuli responsive copolymers.