Study On Enzyme-responsive Linear-dendritic Block Copolymers And Superamphiphiles Using Poly (N,N-dimethylaminoethyl Methacrylate) As A Linear Chain

Poly（N,N-dimethylaminoethyl methacrylate）（PDMAEMA）is a functional polymer with tertiary amine groups,which has p H,temperature,CO₂ and other responsiveness.It has good application prospects in the field of biomedicine.Linear-dendritic block copolymers（LDBCs）have not only the processability of linear chains,but also the versatility of dendrimers,and stimulus-responsive LDBCs have potential applications in drugs and gene carriers.Enzymes are involved in the metabolic processes of all organisms and some enzymes overexpressed in diseased tissues or cells.Therefore,enzyme-responsive polymers have potential application value in targeted release systems of drug.Superamphiphiles refer to amphiphiles that are formed on the basis of noncovalent or dynamic covalent interctions.Such superamphiphiles are easier to introduce functional groups such as stimuli-responsive groups,making superamphiphiles have the characteristics of stimuli responsiveness,reversibility and adaptability.However,at present,the studies on dual-enzyme responsive superamphiphiles polymers are rarely reported.In this thesis,we have synthesized two PDMAEMA-Br linear chains with different molecular weights（M_n=3 k Da,7 k Da）by atom transfer radical polymerization（ATRP）.Then,the phenylalanyl-lysine（Phe-Lys）dipeptide was linked to PDMAEMA-OH throught peptide chemistry,and the end group was converted to an azide-terminated PDMAEMA-b-Phe-Lys-N₃ throught functional group conversion.Finally,the double hydrophilic LDBCs P_mG_n（m=3 k,n=2-3;m=7k,n=3）were prepared by alkynyl/azide（Cu AAC）“click”reaction with the alkynyl-terminated poly（benzyl ether）dendritic unit G_n-alkynyl（n=2-3）.Their structures and molecular weight were characterized by ¹H NMR,FT-IR,ESI-MS and GPC.The P_mG_n（m=3 k,n=2-3;m=7 k,n=3）and a plurality of negatively charged adenosine triphosphates（ATP）can form a superamphiphilic molecules polymers as a result of electrostatic interaction P_mG_n⁺-ATP（m=3 k,n=2-3;m=7 k,n=3）.The self-assembly behavior and enzyme response property of the superamphiphiles polymers were investigated by Zeta-potential and particle size analyzer,¹H NMR,UV spectra,transmission electron microscopy（TEM）and fluorescence spectroscopy.The results showed that P_mG_n-ATP（m=3 k,n=2-3;m=7 k,n=3）can self-assemble into spherical aggregates in aqueous solution.The spherical aggregates disassemble and release loaded hydrophilic small molecule HPTS after treatment with trypsin or alkaline phosphatase（CIAP）.The release rate of the solution treated with trypsin and CIAP was significantly greater than that in the absence of trypsin or CIAP,indicating that the superamphiphiles polymers have dual enzyme responsiveness.