The emergence of treatment approaches that integrate conventional phototherapy with additional adjuvant treatments has garnered considerable interest. In this study, we proposed a complex utilizing Fe and polydopamine as a carrier, co-loaded with the nitric oxide initiator L-arginine (L-Arg) and the photosensitizer indocyanine green (ICG), as a potential strategy for the "photothermal/photodynamic/Chemodynamic/nitric oxide gas therapy" of osteosarcoma. Nanoparticles have the ability to undergo degradation within the mildly acidic conditions present in the tumor microenvironment. Consequently, the resulting release of Fe ions facilitates the consumption of hydrogen peroxide through Fenton/Fenton-like reactions, thereby generating hydroxyl radicals (•OH) that possess potent cytotoxic properties. L-Arg can also be catalyzed by reactive oxygen species (ROS) or NO synthase overexpressed in cancer cells to generate NO, which is not only used for gas therapy (GT), but also as a biological messenger to regulate vasodilation to relieve tumor hypoxia. More importantly, the addition of low-dose near-infrared laser can not only promote the efficiency of the above two reactions, but also achieve PTT/PDT and obtain good synergistic tumor treatment effects. The anti-tumor efficacy of nanoparticles was verified in the 143B mouse osteosarcoma model. This "PTT/PDT/CDT/GT" strategy expands bone tumor treatment options through nanoparticle-mediated enhanced therapy.
Keywords: Chemodynamic therapy; Nitric oxide; Osteosarcoma; Photothermal therapy; Polydopamine; Synergistic therapeutics.
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