Cerium molybdate-doped polyaniline nanoplatform for GSH-depletion-enhanced chemodynamic/NIR-II photothermal synergistic therapy via ferroptosis and immune activation.

Abstract

Chemodynamic therapy (CDT) holds great promise for tumor treatment by catalyzing endogenous hydrogen peroxide (H₂O₂) into cytotoxic reactive oxygen species (ROS). However, its efficacy is severely compromised by glutathione (GSH)-mediated ROS scavenging and intrinsically slow reaction kinetics. To address these limitations, we developed cerium molybdate-doped polyaniline nanoparticles (MoCe@PANI NPs) to enable a synergistic combination of photothermal therapy (PTT) and CDT, thereby triggering immunogenic cell death (ICD) and enhancing antitumor immunity. Mechanistically, MoCe@PANI NPs deplete intracellular GSH and generate abundant ROS via Ce⁴⁺/Mo⁵⁺/Mo⁶⁺-mediated redox cycles, leading to mitochondrial dysfunction and amplified ferroptosis. Crucially, near-infrared II (NIR-II) laser irradiation induces localized hyperthermia, which simultaneously executes PTT and accelerates the Fenton-like reaction kinetics, further intensifying ferroptotic cell death. This combinatorial strategy effectively activates tumor-associated immune responses, achieving effective ablation of primary tumors and eliciting a systemic abscopal effect that suppresses untreated distant metastases. Collectively, this study presents a robust nanoplatform integrating chemodynamic and photothermal therapies for potent cancer immunotherapy.