文献类型：期刊文献

英文题名：Design and evaluation of a phospholipase D based drug delivery strategy of novel phosphatidyl-prodrug

作者：Tao, Xinyi[1];Jia, Ning[1];Cheng, Nenghui[1];Ren, Yuhong[1];Cao, Xuni[1];Liu, Min[1];Wei, Dongzhi[1];Wang, Feng-Qing[1]

机构：[1]East China Univ Sci & Technol, Newworld Inst Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2017

卷号：131

起止页码：1

外文期刊名：BIOMATERIALS

收录：;EI(收录号：20171403519014);WOS:【SCI-EXPANDED(收录号:WOS:000401393600001)】；

基金：This research was financially supported by National Natural Science Foundation of China (81603056).

语种：英文

外文关键词：Phosphatidyl-prodrug; Phospholipase D; Doxorubicin; Triggered release; Reverse multidrug resistance

摘要：A strategy is proposed to design a safe and simple amphiphilic prodrug delivery system, based on the elevated expression of phospholipase D (PLD) in cancer cells. The method utilizes the transphosphatidylation ability of bacterial PLD on alcohol groups and the hydrolysis activity of overexpressed PLD on phospholipids in cancer cells. Doxorubicin (DOX) was selected as a test drug, and the phosphatidyl-doxorubicin (PX) was synthesized by bacterial PLD. The PX prodrug could be readily self assembled to nanoparticles with uniform size and was stable during storage and circulation. The pharmacokinetics and biodistribution investigations indicated DOX could be selectively released from PX in cancer cells triggered by the local overexpressed PLD, and PX could significantly prolong the half-life of DOX in the tumors and decrease the distribution in heart and kidney. Moreover, the PX prodrug enhanced cellular uptake in MCF-7/ADR cells, demonstrating it could reverse the multi-drug resistance. Consequently, the prodrug displayed favorable anticancer efficacy in the MCF-7/ADR xenograft model without the cardiotoxicity and nephrotoxicity of DOX. The results demonstrated that phosphatidyl modification method can be used as an efficient strategy to develop a promising nanoscale drug delivery system for some drugs. (C) 2017 Elsevier Ltd. All rights reserved.