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, t...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.展开更多
基金financially supported by the GDNRC [Guangdong Nature Resource Center](2020)(037)National Natural Science Foundation of China (Nos. 81773642, 52073139)+3 种基金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)。
文摘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.
