Boosting Chemodynamic Therapy via a Synergy of Hypothermal Ablation and Oxidation Resistance Reduction

Chemodynamic therapy (CDT), deemed as a cutting-edge antineoplastic therapeutic tactics, efficaciously suppresses tumors via catalytically yielding hydroxyl radicals (^•OH) in tumor regions. Nevertheless, its biomedical applications are often restricted by the limited hydrogen peroxide (H₂O₂) level and upregulated antioxidant defense. Herein, a versatile nanoreactor is elaborately designed via integrating Cu_2-S and MnO₂ for T₁-weighted magnetic resonance (MR) imaging-guided CDT, synergistically enhanced through hypothermal ablation and oxidation resistance reduction, thereby displaying splendid antitumor efficiency as well as suppression on pulmonary metastasis. The as-synthesized Cu_2-S@MnO₂ nanoreactors afford acid-dependent Cu-based and glutathione (GSH)-activated Mn-based catalytic properties for bimodal CDT. Owing to excellent absorbance at the second near-infrared (NIR-II) window, the Cu_2-S furnishes hypo-photo-thermal therapy (PTT) against tumor growth and ameliorates the catalytic performance for thermal-enhanced CDT. Additionally, MnO₂ significantly downregulates GSH and glutathione peroxidase 4, which synergistically boosts CDT via promoting oxidative stress, simultaneously generating Mn²⁺ for MR contrast improvement and activatable tumor imaging. Therefore, this study proffers a new attempt centered on the collaborative strategy integrating NIR-II hypothermal PTT and synergistically enhanced CDT for tumor eradication.