Photodynamic Therapy Initiated Ferrotherapy of Self-Delivery Nanomedicine to Amplify Lipid Peroxidation via GPX4 Inactivation
| Autor: | Lin-Ping Zhao, Shao-Yi Chen, Rong-Rong Zheng, Xiao-Na Rao, Ren-Jiang Kong, Chu-Yu Huang, Yi-Bin Liu, Youzhi Tang, Hong Cheng, Shi-Ying Li |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | ACS Applied Materials & Interfaces. 14:53501-53510 |
| ISSN: | 1944-8252 1944-8244 |
| Popis: | Lipid peroxide (LPO) is the hallmark of ferroptosis, which is a promising antitumor modality for its unique advantages. However, a cellular defense system would weaken the antitumor efficacy of ferrotherapy. Herein, a GPX4 inhibitor of ML162 and a photosensitizer of chlorine e6 (Ce6) are used to prepare the self-delivery nanomedicine (C-ML162) through hydrophobic and electrostatic interactions to enhance ferroptosis by photodynamic therapy (PDT). Specifically, carrier-free C-ML162 improves the solubility, stability, and cellular uptake of antitumor agents. Upon light irradiation, the internalized C-ML162 generates large amounts of reactive oxygen species (ROS) to oxidize cellular unsaturated lipid into LPO. More importantly, C-ML162 can directly inactivate GPX4 to enhance the accumulation of toxic LPO, inducing ferroptotic cell death. Additionally, C-ML162 is capable of accumulating at a tumor site for effective treatment. This self-delivery system to amplify lipid peroxidation via GPX4 inactivation for PDT initiated ferrotherapy might provide an appealing strategy against malignancies. |
| Databáze: | OpenAIRE |
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