Iridium Oxide-Doped Calcium Phosphate Nanoparticles for Chemodynamic Therapy of Cancer

Abstract

Chemodynamic therapy (CDT), a non-invasive cancer treatment strategy, selectively induces cancer cell death without harming normal cells. However, CDT's efficacy is limited by the inadequate levels of endogenous hydrogen peroxide (H2O2) in tumor cells and the powerful antioxidant system glutathione (GSH). To overcome this obstacle, the study introduces a nanointelligent platform (IrOx-CaP@PTX NPs) incorporating paclitaxel (PTX), a cytotoxic agent, employing glucose oxidase (GOx) as a scaffold to generate degradable calcium phosphate (CaP) nanoparticles doped with iridium oxide (IrOx) via physisorption. To stabilize the nanosystems and enable them to target tumor cells, hyaluronic acid (HA) was finally modified on their surface. By conducting both in vitro and in vivo experiments, it was revealed that GOx functioned as an enzymatic accelerator, producing H2O2 and gluconic acid through glucose metabolism within cancerous cells. This process starved the tumor cells but also provided a continuous supply of H2O2 and an acidic environment for the subsequent CDT. Furthermore, the released IrOx used its peroxidase activity (POD) to generate hydroxyl radicals (•OH) from H2O2 and consume intracellular reducing GSH through its valence exchange, thus further enhancing the efficacy of CDT. Finally, PTX acted synergistically with CDT as a chemotherapeutic agent for treatment. In summary, the IrOx-CaP@PTX NPs accomplished a multimodal treatment strategy encompassing GOx-mediated metabolic restriction, self-generation of H2O2, enhanced elimination of GSH for improved CDT, and PTX-induced chemotherapy. This comprehensive approach demonstrated superior tumor growth inhibition and reduced adverse effects in vivo studies. In conclusion, this study provides a non-invasive therapeutic strategy for the synergistic treatment of cancer.