Fe3+ loaded mastoparan M - ICG nanoassemblies for synergistic breast cancer therapy via photothermal and chemodynamic therapy-assisted oxidation stress

Traditional chemotherapy for breast cancer faces limitations, including poor drug bioavailability, multidrug resistance, and severe systemic side effects. Therefore, a carrier-free nanodrug composed of Mastoparan M (Mast-M, derived from Wasp toxin), FDA-approved near infrared fluorescence dye (indocyanine green, ICG), and biosafe ion Fe 3+ was developed to achieve photothermal (PTT) and synergistic chemodynamic therapy (CDT)-assisted oxidation therapy. Once accumulated within tumor sites by enhanced permeability and retention (EPR) effects, the Mast-M/Fe 3+ /ICG rapidly dissociates in response to elevated glutathione (GSH), releasing Fe 2+ , ICG, and Mast-M. Mast-M efficiently triggers reactive oxygen species (ROS) generation to induce mitochondrial membrane potential disruption. Fe 2+ -mediated CDT further amplifies oxidative stress, accompanied by GSH consumption and lipid peroxide (LPO) accumulation. Under laser irradiation, ICG generates hyperthermia to enhance oxidative stress. In vitro and in vivo studies demonstrated enhanced antitumor efficacy with reduced systemic toxicity. Together, these findings highlight the potential of carrier-free nanodrugs for oxidative stress-based breast cancer therapy.