CoFe2O4-Based Multifunctional Nanozymes Remodel Tumor Redox Balance for Enhanced Osteosarcoma Treatment

Background Developing nanodrugs with passive targeting capabilities that can effectively overcome the oxidative-redox homeostasis-inhibiting microenvironment of tumors offers new insights into the precise treatment of osteosarcoma.Methods CoFe2O4 nanoparticles were synthesized via the hydrothermal method and modified with polyethylene glycol 4000 on their surface, obtaining CF@P nanozymes with multi-catalytic activities similar to catalase (CAT), peroxidase (POD), oxidase (OD), and glutathione peroxidase (GPx). These nanozymes could overcome the hypoxic microenvironment and redox homeostasis in osteosarcoma treatment.Results CF@P has a size of approximately 100 nm and can stably exist under physiological conditions. It exhibits excellent photothermal effects under near-infrared II (1064 nm) laser irradiation, synergistically enhancing its catalytic activity. CF@P alleviates hypoxia by decomposing endogenous H2O2 within tumors to generate oxygen and hydroxyl radicals (·OH). Meanwhile, it consumes reduced glutathione (GSH) within tumors, inducing ferroptosis and apoptosis. CF@P exhibits low toxicity to normal cells (HUVEC) and selective killing ability against osteosarcoma cells (U2OS). In vivo, it accumulates in tumor tissues via the enhanced permeability and retention (EPR) effect, significantly inhibiting tumor growth in combination with photothermal therapy without causing significant organ toxicity, thereby prolonging the survival of tumor-bearing mice.Conclusion The CF@P nanozyme integrates the properties of multi-enzyme catalysis and photothermal therapy, disrupting the oxidative-redox homeostasis of tumor tissues, generating highly toxic hydroxyl radicals, and efficiently inducing apoptosis in osteosarcoma cells. This approach provides a new, efficient, and safe strategy for the precise treatment of hypoxic solid tumors like osteosarcoma.