Hybrid cell membrane-functionalized biomimetic nanozymes: Triple-modal CDT/PTT/PDT therapy activates apoptosis, ferroptosis, pyroptosis, and cuproptosis to eliminate breast cancer

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Breast cancer is a highly prevalent malignant tumor among women. Traditional therapies suffer from inherent toxicity and drug resistance issues, while novel monomodal treatments have also failed to deliver satisfactory outcomes. To address these limitations, we developed a biomimetic nanoparticle system by preparing polydopamine (PDA)-modified Cu 2 [Fe(CN) 6 ] bimetallic nanozymes loaded with IR783 (a near-infrared photosensitizer) and encapsulated in hybrid cell membranes (TRCM), aiming to achieve highly efficient and precise breast cancer treatment. TRCM endowed the nanoparticles with immune evasion and breast cancer targeting capabilities, enhancing their accumulation at the tumor site. Simultaneously, TRCM@IPCu nanoparticles could deplete glutathione (GSH) to enhance reactive oxygen species (ROS) production, alleviate tumor hypoxia, and generate heat to initiate chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT), achieving synergistic CDT/PTT/PDT treatment. Mechanistic studies confirmed that TRCM@IPCu induced tumor cell death through multiple pathways including apoptosis, ferroptosis, pyroptosis, and cuproptosis, and significantly inhibited tumor growth in vivo. This approach offered novel insights for developing multifunctional nanozyme-based anti-breast cancer therapeutics.