Abstract:

A polyethylene glycol （PEG） derivative PBA-PEG-SA， which connects phenylboronic acid （PBA） with an amide bond at one end and stearic acid （SA） with an ester bond at the other end， is synthesized by substitution reaction and esterification reaction. And a liposome with pH response characteristics is prepared by co-assembly of PBA-PEG-SA with distearyl choline phosphate （DSCP） and cholesterol （CH）. When PBA-PEG-SA， cholesterol and DSCP are assembled at a mass ratio of 1∶3∶10， the particle size of the prepared liposome is 115 nm， and it could maintain good particle size stability within 20 d. In addition， the liposome has good biocompatibility. When the concentration reaches 800 μg/mL， the survival rate of mouse embryonic fibroblast （NIH-3T3）and hepatoma cell （HepG2） can reach more than 90%. At the same time， after loading doxorubicin （Dox）， compared with DSCP liposomes （Lip/Dox）， Fru/PBA/Lip/Dox liposomes modified with PBA and coated with Fru can effectively enhance the cytotoxicity of HepG2， reduce the toxicity to normal cells NIH-3T3， and improve the endocytosis of cells to drug-loaded liposomes due to the selective binding of phenylboronic acid and fructose. Therefore， the liposomes co-assembled by DSCP and PBA-PEG-SA have good pH response performance and enhance the enrichment ability of liposomes in tumor tissue， which will have good application prospects in the field of tumor therapy.

Key words: pH response, Phenylboronic acid, Co-assembled liposomes, Drug delivery