Polymeric prodrug for bio-controllable gene and drug co-delivery  

作　　者：Huizhen Jia Si Chen Renxi Zhuo Jun Feng Xianzheng Zhang 

机构地区：[1]Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, China [2]School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072, China

出　　处：《Science China Chemistry》2016年第11期1397-1404,共8页中国科学（化学英文版）

基　　金：supported by the National Natural Science Foundation of China (21374085, 21174110, 51233003);the Natural Science Foundation of Hubei Province of China (2014CFB697);the Fundamental Research Funds for the Central Universities (2042014kf0193)

摘　　要：A polymeric polyethylenimine(PEI)-based prodrug of anticancer doxorubicin(DOX)(PEI-hyd-DOX) was designed by attaching DOX to PEI via an acid-labile hydrazone bond, for the achievement of biocontrollable gene and drug co-delivery in response to the intracellular acid microenvironments in the late endosome/lysosome compartments. The cytotoxicity of PEI-hyd-DOX was evaluated by the MTT assay and the cellular uptake was monitored using confocal laser scanning microscopy. The polymeric prodrug can respond with a high sensitivity to the specific acid condition inside cells, thus permitting the precise biocontrol over intracellular drug liberation with high drug efficacy. The chemical attachment of drug molecules also led to the relatively reduced toxicity and the enhanced transfection efficiency compared with parent PEI. The resulting data adumbrated the potential of PEI-hyd-DOX to co-deliver DOX and therapeutic gene for the combination of chemotherapy and gene therapy.A polymeric polyethylenimine（PEI）-based prodrug of anticancer doxorubicin（DOX）（PEI-hyd-DOX） was designed by attaching DOX to PEI via an acid-labile hydrazone bond, for the achievement of biocontrollable gene and drug co-delivery in response to the intracellular acid microenvironments in the late endosome/lysosome compartments. The cytotoxicity of PEI-hyd-DOX was evaluated by the MTT assay and the cellular uptake was monitored using confocal laser scanning microscopy. The polymeric prodrug can respond with a high sensitivity to the specific acid condition inside cells, thus permitting the precise biocontrol over intracellular drug liberation with high drug efficacy. The chemical attachment of drug molecules also led to the relatively reduced toxicity and the enhanced transfection efficiency compared with parent PEI. The resulting data adumbrated the potential of PEI-hyd-DOX to co-deliver DOX and therapeutic gene for the combination of chemotherapy and gene therapy.

关 键 词：gene/drug co-delivery hydrazone bond p H-sensitivity polymeric prodrug transfection efficiency 

分 类 号：TQ460.1[化学工程—制药化工]