Reactive Oxygen-Primed and Autophagy Inhibition-Sensitized Ferroptosis Combined with Photothermal Ablation for Tumor Therapy

• DOI: 10.1021/acsmaterialslett.3c00536
• Publication Date: 2023-07-24T11:30:21Z
• Authors: Dihai Gu; Min Liu; Hongshuai Wu; Jiannan Mao; Jinzhong Hu; Xu Zhi; Zhaohan Wang; Xinyue Shang; Xiongwei Deng; Yihong Wang
• Keywords: GPX4

The accumulation of lethal reactive oxygen species (ROS) and lipid peroxidation (LPO) is the hallmark ferroptosis therapy. However, a single process has difficulty inhibiting tumor progress. Autophagy inhibitors can inhibit autophagy by blocking automatic capsules closing self-protection pathway oxidative stress, which promotes Fenton or Fenton-like reaction to enhance LPO accumulation. Herein, versatile core–shell nanoparticle system, denoted as CQ/PEG-CuS@hMnO2, was designed synthesized for oxygen-primed inhibition-sensitized ferroptosis. Glutathione (GSH) depletion CuS@hMnO2 caused inactivation glutathione peroxidase 4 (GPX4), key defense protein Highly toxic ROS were generated Mn2+-mediated reinforce intracellular directly resulting in LPO. Meanwhile, played an indispensable effect ferroptosis; thus, loading chloroquine (CQ) inhibitor aimed sensitivity Besides, excellent photothermal therapy could be triggered NIR irradiation (980 nm) due CuS core. In vivo vitro experiment results demonstrated that CQ/PEG-CuS@hMnO2 presented anticancer human breast cancer model, proving ferroptosis/photothermal dual-inductive strategy promising combat malignant tumors.