Self-Amplification of Tumor Oxidative Stress with Degradable Metallic Complexes for Synergistic Cascade Tumor Therapy
Gui Chen, Yuanyuan Yang, Qing Xu, Mingjian Ling, Huimin Lin, Wen Ma, Rui Sun, Yuchun Xu, Xiqiang Liu, Nan Li, Zhiqiang Yu, Meng Yu
Abstract
The ferroptosis effect has been illuminated with a clear Fenton reaction mechanism that converts endogenous hydrogen peroxide (H2O2) into highly oxidative hydroxyl radicals (·OH) in ROS-amplified tumor therapy. This ferroptosis-related oxidation effect was then further enhanced by the enzyme-like roles of cisplatin (CDDP). This CDDP-induced apoptosis was promoted in reverse by ferroptosis via the depletion of glutathione (GSH) and prevention of DNA damage repair. Here, we have developed degradable metallic complexes (PtH@FeP) containing an Fe(III)-polydopamine (FeP) core and HA-cross-linked CDDP (PtH) shell, exaggerating in situ toxic ROS production via the synergistic effect of CDDP and Fe(III). Taken together, the rationally designed PtH@FeP provided a new strategy for self-amplified synergistic chemotherapy/ferroptosis/photothermal therapy (PTT) antitumor effects with a reduced dosage that facilitates clinical safety.