Isoliquiritigenin-Loaded\nPlatinum(IV) Prodrug Micelles\nInduce Sustained Endoplasmic Reticulum Stress for Promoting Cisplatin\nChemosensitivity in Ovarian Cancer

Platinum-based\nchemotherapy is the cornerstone of ovarian\ncancer\n(OC) treatment. However, decrease of cellular concentration of the\ndrug, glutathione (GSH)-mediated drug inactivation, and severe toxic\nside effects contribute to its clinical chemotherapy failure. Cisplatin\nhas the ability to induce endoplasmic reticulum stress (ERS) production\nin OC, and sustained ERS can potentiate the cytotoxic effects of chemotherapy.\nHerein, platinum(IV) prodrug nanoparticles (IPD NPs) are prepared\nas nanocarriers of isoliquiritigenin (ISL, traditional Chinese medicine)\nwith redox-responsive degradation properties and synergistic ERS amplification\nfor enhanced OC treatment. Notably, IPD NPs contain docosahexaenoic\nacid (DHA) which enhanced cellular uptake as well as generated reactive\noxygen species (ROS), thereby breaking redox homeostasis and further\naugmenting the effect of ERS. This current strategy of sustained ERS\namplification for enhanced cisplatin-based chemotherapy overcomes\nthe low cellular uptake, GSH-mediated drug detoxification, avoids\nthe dose-dependent nephrotoxicity of cisplatin, and is promising for\nOC treatment.