ROS Self-Supply Nanoplatform Based on Fenton Catalyst for Chemodynamic and Immunotherapy: Reprogramming Cold Tumor...

The immunosuppressive tumor microenvironment (TME) severely limits the clinical efficacy of immunotherapy, largely due to the prevalence of "cold tumors" with minimal T cell infiltration. To address this, we developed a reactive oxygen species (ROS) self-supplying nanoplatform (HA-PGMC) by in situ growing copper peroxide (CuO₂) nanodots and loading glucose oxidase (GOx) within a mil-100 metal-organic framework (MOF). HA-PGMC exploits the catalytic cascade between released Fe^{2 +} and Cu⁺ ions to generate abundant •OHs (•OH) under acidic and glucose-rich tumor conditions, thereby amplifying oxidative stress. Meanwhile, Cu^{2 +} ions deplete glutathione (GSH), further enhancing ROS accumulation. In vitro studies demonstrate that HA-PGMC induces significant ROS production, GSH depletion, lipid peroxidation, mitochondrial dysfunction, and robust antitumor effects with minimal toxicity to normal cells. Importantly, HA-PGMC triggers immunogenic cell death (ICD) by promoting CRT exposure and HMGB1 release, effectively converting "cold" tumors into "hot" tumors. This enhanced immune activation paves the way for synergistic combination with immune checkpoint blockade therapy. Collectively, this ROS-amplifying nanoplatform offers a promising strategy for overcoming the limitations of current cancer immunotherapy by simultaneously inducing potent chemodynamic therapy (CDT) and reprogramming the tumor immune microenvironment.