Integrating of lipophilic platinum(IV) prodrug into liposomes for cancer therapy on patient-derived xenograft model  

作　　者：Zibo Li Qing Xu Xuefeng Lin Kunyi Yu Ling Lin Yangjia Liu Zhiqiang Yu Tiancai Liu Dixian Luo 

机构地区：[1]Department of Laboratory Medicine,Huazhong University of Science and Technology Union Shenzhen Hospital(Nanshan Hospital),Shenzhen 518000,China [2]Guangdong Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515,China [3]School of Laboratory Medicine and Biotechnology,Institute of Antibody Engineering,Southern Medical University,Guangzhou 510515,China

出　　处：《Chinese Chemical Letters》2022年第4期1875-1879,共5页中国化学快报（英文版）

基　　金：financially supported by the GDNRC [Guangdong Nature Resource Center](2020)(037);National Natural Science Foundation of China (Nos. 81773642, 52073139);the Natural Science Foundation of Guangdong Province (No. 2019A1515011619);Guangdong Provincial Science and Technology Department (No.2016A030311015);the Key R&D Plan of Chenzhou (No.ZDYF202008);the Discipline Leader Startup Fund of Huazhong University of Science and Technoloy Union Shenzhen Hospital (No.YN2021002)。

摘　　要：Platinum-based anticancer agents such as cisplatin and its analogues are widely used for treating multiple cancers. However, due to the inferior water-solubility, chemoresistance and consequent adverse side effects, their clinical applications are limited. Herein, choles Pt(IV), a lipophilic platinum(IV) prodrug was synthesized for manufacture of Choles Pt(IV)-Liposomes aiming to resolve the predefined obstacles encountered by platinum drugs. Following systematic screening, Choles Pt(IV)-Liposomes showed a small particle size(105.6 nm), the rapid release of platinum(Pt) ions, and notable apoptosis of cancer cells.In addition, according to the fluidity and safety results of animal experiments in mice, Choles Pt(IV)-Liposomes also showed better therapeutic effect, which significantly inhibited the growth of patientderived xenograft tumors of hepatocellular carcinoma with an inhibition ratio of 80.7%, and effectively alleviated the drug toxicity brought by traditional platinum drugs. Overall, this study provides a promising route to enhance the therapeutic efficiency of platinum drugs in cancer treatment.

关 键 词：Lipophilic platinum(IV)prodrug Liposome Cancer therapy Drug delivery Patient-derived xenograft 

分 类 号：TQ460.1[化学工程—制药化工]