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

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.