Facile preparation of pH-responsive PEGylated prodrugs for activated intracellular drug delivery  

作　　者：Yue Song Dian Li Jinlin He Mingzu Zhang Peihong Ni 

机构地区：[1]College of Chemistry, Chemical Engineering and Materials Science, State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials,Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, Suzhou Key Laboratory of Macromolecular Design and Precision Synthesis,Soochow University

出　　处：《Chinese Chemical Letters》2019年第12期2027-2031,共5页中国化学快报（英文版）

基　　金：the financial supports from the National Natural Science Foundation of China(No.21374066);the Major Program of the Natural Science Project of Jiangsu Higher Education Institutions(No.15KJA150007);Natural Science Foundation of Jiangsu Province(No.BK20171212);the Project Funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions;Soochow-Waterloo University Joint Project for Nanotechnology from Suzhou Industrial Park

摘　　要：PEGylated prodrug,covalent attaching polyethylene glycol(PEG) polymer chains to therapeutic drugs,is one of the most promising techniques to improve the water-solubility,stability,and therapeutic effect of drugs.In this study,three PEGylated acid-sensitive prodrugs DOX-PEG-DOX with different molecular weights,were prepared via Schiff-base reaction between aldehyde-modified PEG and the amino groups of doxorubicin(DOX).This kind of amphiphilic polymeric prodrug could be self-assemble into nanoparticles in aqueous solution.The average particle size and morphologies of the prodrug nanoparticles under different pH conditions were observed by dynamic light scattering(DLS) and transmission electron microscopy(TEM),re s pectively.It turned out that the nanoparticles could be kept stable in the physiological environment,but degraded in acidic medium.Subsequently,we also investigated in vitro drug release behavior and found that the prodrug had acid-sensitive property.The cytotoxicity and intracellular uptake assays revealed that the prodrugs could rapidly internalized by HeLa or HepG2 cells to release DOX and effectively inhibited the proliferation of the tumor cells,which have the potential for use in cancer therapy.PEGylated prodrug,covalent attaching polyethylene glycol(PEG) polymer chains to therapeutic drugs,is one of the most promising techniques to improve the water-solubility,stability,and therapeutic effect of drugs.In this study,three PEGylated acid-sensitive prodrugs DOX-PEG-DOX with different molecular weights,were prepared via Schiff-base reaction between aldehyde-modified PEG and the amino groups of doxorubicin(DOX).This kind of amphiphilic polymeric prodrug could be self-assemble into nanoparticles in aqueous solution.The average particle size and morphologies of the prodrug nanoparticles under different pH conditions were observed by dynamic light scattering(DLS) and transmission electron microscopy(TEM),re s pectively.It turned out that the nanoparticles could be kept stable in the physiological environment,but degraded in acidic medium.Subsequently,we also investigated in vitro drug release behavior and found that the prodrug had acid-sensitive property.The cytotoxicity and intracellular uptake assays revealed that the prodrugs could rapidly internalized by HeLa or HepG2 cells to release DOX and effectively inhibited the proliferation of the tumor cells,which have the potential for use in cancer therapy.

关 键 词：Polyethylene glycol DOXORUBICIN PRODRUG Schiff-base reaction pH-Responsiveness 

分 类 号：TQ460.4[化学工程—制药化工]