Near-infrared light-triggered nitric oxide-enhanced chemodynamic and photothermal therapy on magnesium alloy implants in osteosarcoma

This work fabricated FeOOH/arginine composite coatings firmly bonded onto Mg alloy substrates, which greatly enhanced the corrosion resistance of biodegradable magnesium implants. • The composite coating achieves NIR and TME dual-responsive controlled NO release, and the PTT-CDT-NO synergistic therapy suppresses core oncogenic signaling pathways to induce efficient osteosarcoma cell death, while low-concentration NO facilitates anti-inflammation and angiogenesis. • By utilizing the concentration-dependent bidirectional effects of NO, the constructed multifunctional coating offers a simple and low-cost design strategy for intelligent magnesium alloy implants toward clinical postoperative bone tumor therapy. Osteosarcoma is prone to recurrence after surgery and is accompanied by extensive bone defects. Traditional treatment methods struggle to achieve tumor suppression and bone repair simultaneously. Degradable magnesium alloys are ideal bone implant materials, yet they have drawbacks, including overly rapid degradation and a lack of anti-tumor activity. Although nitric oxide (NO) shows promise for its anti-inflammatory and regenerative properties, its clinical translation is limited by its short half-life and uncontrolled release, which do not meet the postoperative requirements for osteosarcoma. Herein, in this work, a porous PEO (plasma electrolytic oxidation) coating was first prepared on Mg alloys to improve corrosion resistance, and then Fe 2+ and L-arginine were simultaneously introduced to synthesize the FeOOH-Arg coating in situ, which was then coated with polydopamine to obtain a responsive composite coating. This composite coating achieved interfacial bonding and seals the PEO porous structure through covalent bonding, and can realize the controllable release of NO and reactive oxygen species (ROS) with near-infrared light irradiation and tumor microenvironment, not only synergistically combining the photothermal therapy (PTT) and chemodynamic therapy (CDT) to induce the apoptosis of osteosarcoma cells efficiently, but also regulate the immune microenvironment and promote angiogenesis both in vitro and in vivo. This work offers a novel, feasible, multifunctional modified magnesium alloy implant for integrated anti-tumor and bone-regeneration treatment following osteosarcoma surgery.