Tumor microenvironment-responsive nanoplatform for self-supplying H₂O₂-propelled process with monitoring and precision therapy.

Chemodynamic therapy (CDT) has been extensively explored as an emerging light-independent antitumor strategy, but its efficacy is severely constrained by insufficient level of hydrogen peroxide (H₂O₂) in vivo as well as the lack of monitoring of catalytic processes. In this work, a tumor microenvironment (TME)-responsive nanoplatform (IrO₂ NPs@GOD/DOX@DMON) was constructed for self-supplying H₂O₂-propelled process with monitoring and precision therapy. Dendritic mesoporous organosilica nanoparticles (DMONs) acted as carriers to achieve the glutathione (GSH)/pH-responsive drug release. The cascade catalytic process was initiated by glucose oxidase (GOD), which consumed intratumoral glucose to generate the sustained H₂O₂. Iridium oxide nanoparticles (IrO₂ NPs) acted as a robust nanozyme, catalyzing the in-situ-generated H₂O₂ to produce highly toxic reactive oxygen species (ROS) for CDT. Meanwhile, the ROS level served as an indicator for monitoring of CDT, using the colorimetric probe (TMB) for in vitro catalytic activity assessment and fluorogenic probe (DCFH-DA) for in cell imaging of ROS. Notably, IrO₂ NPs also exhibited excellent photothermal properties, which could further enhance the therapeutic effect. Related data revealed that nanoplatform possessed remarkable antitumor efficacy in vivo, and the synergistic trimodal therapy exhibited significantly stronger tumor suppression than any single treatment modality. This system integrates H₂O₂ self-supplying, catalytic processes tracking, and synergistic therapy, presenting a promising paradigm for precise therapy.