Se-Fe Hydrogel with Switchable Hyperthermia for Osteosarcoma Therapy.

Introduction: Clinical treatment of osteosarcoma remains challenging because of residual tumor-associated recurrence, bacterial infection, and insufficient bone reconstruction. To address these challenges, a selenium-iron Prussian blue nanocube (FeSePB) was designed and encapsulated within a thermoresponsive hydrogel for osteosarcoma therapy. Methods: The FeSePB nanocube functions as an efficient photothermal conversion agent, producing localized heating under near-infrared (NIR) irradiation and enabling controlled softening of the hydrogel after implantation under laser irradiation. Following administration into the osteosarcoma site, initial NIR irradiation triggered hydrogel softening and rapid release of FeSePB, resulting in elevated local temperature that eliminated residual tumor cells and achieved antibacterial effects through photothermal therapy (PTT). Concurrent selenium release further inhibited bacterial growth, reducing infection risk. Results: In vitro experiments demonstrated that sustained mild PTT induced moderate hyperthermia, which supported bone regeneration. In vivo animal experiments demonstrated remarkable tumor growth inhibition, with inhibition rates of about 90.67% compared with the control group. Thus, the FeSePB hydrogel demonstrated NIR-switchable temporal regulation, enabling integrated anti-tumor, anti-infective, and pro-osteogenic functions during osteosarcoma treatment. Conclusion: This strategy offers a multifunctional therapeutic platform that simultaneously addresses tumor proliferation, infection, and bone loss, highlighting its potential for clinical translation.