Studies On Enzymes Linked With Phenylalanyl-lysine Dipeptide And PH Responsive Linear-dendritic Block Copolymers

Amphiphilic linear-dendritic block copolymers(LDBCs)have been widely used in biomedical field due to their unique self-assembly characteristics.Enzyme and pH-responsive polymers have the advantages of targeting drug delivery and biocompatibility,which make them potentially useful in the field of biomedicine.However,there are few reports on enzymatic and pH-responsive LDBCs.In this paper,three new generations of enzymatic and PH responsive linear-dendritic block copolymers(LDBCs)PNVP-Phe-Lys(Fmoc)-b-G_n(n=1-3)based on hydrophilic linear poly(N-vinylpyrrolidone)(PNVP)and hydrophobic dendritic aliphatic polyester of 2,2’-bis(hydroxymethyl)propionic acid(bis-MPA)linked by a phenylalanyl-lysine dipeptide were synthesized by reversible addition-fragmentation chain transfer radical polymerization(MADTX/RAFT)mediated by xanthate and“chain-first method”.The results of ~1H NMR and GPC characterization show that the synthesized LDBCs have controllable molecular weight and narrow molecular weight distribution(PDI≤1.25).The results show that the second and third generation LDBCs can self-assemble into spherical micelles in aqueous solution to encapsulate lipophilic dye Nile red or paclitaxel.When trypsin or pH=5.0 buffer solution is added,the encapsulated Nile red or paclitaxel molecules were released from micelle assembly.The higher the enzyme concentration,the faster disassembly rate of the micelles and the release rate of the drug.In addition,the rate of micelle disassembly decreases with the increase of the generation of the copolymers.The loading rate and encapsulation rate of paclitaxel-loaded micelles were 5.5%and 81.36%,respectively,determinedby ultraviolet spectrophotometry.Compared with single stimulus response,the release rate and amount of Nile red or paclitaxel were significantly increased after treatment with trypsin in pH 5.0 buffer solution.The results showed that the micelles of PNVP-Phe-Lys(Fmoc)-b-G_n block copolymer had dual responsiveness of enzyme and pH.