NIR-II reinforced intracellular cyclic reaction to enhance chemodynamic therapy with abundant H₂O₂ supply.

Abstract

Chemodynamic therapy (CDT) is an ideal therapeutic modality with endogenous H₂O₂ as stimulus. Most intracellular H₂O₂ supplement strategies for improving CDT efficiency are strongly rely on oxygen participation, and the hypoxia tumor microenvironment impairs their performance. Here we develop a self-assembled metal-organic coordinated nanoparticle Cu-OCNP/Lap with NIR-II reinforced intracellular cyclic reaction to enhance CDT efficiency. Cu-OCNP/Lap is synthesized using Cu²⁺ as nodes and 1,4,5,8-tetrahydroxyanthraquinone (THQ) and banoxantrone dihydrochloride (AQ4N) as ligands, with β-lapachone (β-Lap) loading to conduct intracellular cyclic reaction. Cu-OCNP/Lap has good photothermal effect at NIR-II window, and the corresponding local temperature increase speeds blood flow and supplies sufficient oxygen at tumor site to reinforce β-Lap cyclic reaction with abundant H₂O₂ generation. Cu⁺ is released from Cu-OCNP/Lap in response to glutathione (GSH) and triggers CDT. Sufficient intracellular H₂O₂ supply enhances CDT effect and demonstrates good suppressions for tumor growth. This design offers a promising strategy to enhance CDT efficiency.