High-performance pyrite nano-catalyst driven photothermal/chemodynamic synergistic therapy for Osteosarcoma

Abstract Osteosarcoma (OS) is an aggressive bone tumor with strong invasiveness, rapid metastasis and dreadful mortality. Chemotherapy is commonly used approach for OS treatment but was limited by the development of drug resistance and long-term adverse effects. To date, OS still lack the curative treatment. Herein, we fabricated pyrite-based nanoparticles (FeS 2 @CP NPs) as synergetic therapeutic platform by integrating photothermal therapy (PTT) and chemo-dynamic therapy (CDT) into one system. The synthetic FeS 2 @CP NPs showed superior Fenton reaction catalytic activity. FeS 2 @CP NPs-based CDT efficaciously eradicated the tumor cells by initiating double killing-effect of apoptosis and ferroptosis. Furthermore, the generated heat from FeS 2 @CP under near-infrared region II (NIR II) laser irradiation could not only inhibit tumors growth, but also promote tumor cell apoptosis and ferroptosis by accelerating •OH production and GSH depletion. Finally, the photothermal/NIR II-enhanced CDT synergistic therapy show excellent osteosarcoma treatment effect both in vitro and in vivo with negligible side effects. Overall, this work provided a high-performance and multifunctional Fenton catalyst for osteosarcoma synergistic therapy, which provided a pathway for the clinical application of PTT augmented CDT.