Study On Temperature?Enzyme And PH Responsive Linear Dendritic Block Copolymers Based On Poly(N,N-Dimethylaminoethyl Methacrylate)

Poly(N,N-dimethylaminoethyl methacrylate)(PDMAEMA)is a functional polymer with temperature,p H and CO₂responsiveness,and good biocompatibility and low toxicity.It is a smart polymer material with medical prospects.Linear-dendritic block copolymers(LDBCs)have not only the processability of traditional linear block copolymers but also the highly branched structure and versatility of dendrimers,and stimulus responsive amphiphilic linear-dendritic block copolymers have very good promising applications in drug delivery systems.Among the various stimulus-responsive factors,temperature,enzymes and p H are the environmental conditions of the cell itself,which are easier to achieve than other factors required for drug release.However,there are few reports on temperature,enzyme and p H stimulus-responsive amphiphilic LDBCs.In this paper,the first and second generations of amphiphilic LDBCs,PDMAEMAm-Phe-Lys-b-G_n(m=2k,18k,n=1,2)based on hydrophilic linear PDMAEMA with different molecular weights and hydrophobic dendritic aliphatic polyester of ketal terminated 2,2'-bis(hydroxymethyl)propionic acid(bis-MPA)linked by a phenylalanyl-lysine dipeptide,are designed and synthesized by atom transfer radical polymerization(ATRP)or reversible addition-fragmentation chain transfer(RAFT)radical polymerization.Their structure and molecular weight were characterized by ¹H NMR spectra and GPC.The self-assembly behavior and temperature,enzyme and p H responsive properties of these block copolymers in aqueous solution were investigated by ¹H NMR spectra,fluorescence spectra and transmission electron microscopy(TEM).The results show that the block copolymers have low critical solution temperature(LCST).PDMAEMA_2k-Phe-Lys-b-G₂can self-assemble to form spherical micelles in aqueous solution.The micelles can encapsulate the hydrophobic anticancer drug doxorubicin.The maximum drug loading and entrapment efficiency of PDMAEMA_2k-Phe-Lys-b-G₂micelles for doxorubicin were 20.5%and 82.3%,respectively.Under the action of trypsin or in p H 5 and p H 5 buffer solution containing trypsin,drug-loaded micelles can disassemble and release the contained drug,and the higher the concentration of the enzyme,the higher the drug release rate.Drug release rate was the largest in the enzyme containing p H 5 buffer solution,followed by p H 5 medium,the smallest in the p H 7.4buffer solution containing enzyme,indicating that PDMAEMA_2k-Phe-Lys-b-G₂micelles had temperature,enzyme and p H responsiveness.