In Situ Supramolecular Self‐Assembly of Pt(IV) Prodrug to Conquer Cisplatin Resistance

• DOI: 10.1002/adfm.202101826
• Publication Date: 2021-04-24T06:18:13Z
• Authors: Qian Wang; Meng Xiao; Dianyu Wang; Xiaoxue Hou; Jie Gao; Jinjian Liu; Jianfeng Liu
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

Abstract Drug resistance has always been a huge challenge that should be urgently conquered to improve the efficacy of anticancer drugs. Herein, synergistic Pt(IV) prodrug, Npx‐p p ‐Pt(IV), is proposed, combining dual responsive behavior with drug resistance‐related pathways deactivation. First, ‐Pt(IV) can in situ form supramolecular self‐assembly nanofiber structure on cancer cell surface triggered by phosphatase, which confines tumor and effectively enhances cellular uptake cisplatin, resulting high selectivity an extremely low non‐targeted cytotoxicity. After being endocytosed, shows glutathione‐responsive cisplatin release reverses IC 50 cisplatin‐resistant cells sensitive ones. Second, obtained prodrug significantly damage cisplatin‐resistance through cyclooxygenase‐2 nuclear factor‐kappa B‐mediated apoptosis pathways, benefit from integration naproxen into prodrug. The vivo experiment demonstrates inhibition rate 80%. Therefore, multispecific derivative, believed new strategy conquer for clinical care.