BFO@Au leveraged membrane necrotherapy: Rapid tumor eradication via membrane oxidation and immune activation

The rapid development of nanomedicine has significantly improved the targeting and biosafety of cancer therapy. However, most current nanotherapeutics require 4-24 h of intracellular delivery and signaling responses, leading to delayed responses, increased risks of resistance and metastasis. Achieving efficient tumor cell killing within minutes holds promise for overcoming these limitations and enabling more thorough tumor elimination. In this study, we synthesized a nanosheet material, Bi₂Fe₄O₉@Au (BFO@Au NSs), which integrates membrane thiol-targeting recognition with potent oxidative-damage capability. By efficiently depleting sulfhydryl groups on the surface of tumor cell membranes and disrupting membrane functional proteins within minutes, BFO@Au NSs rapidly induces membrane dysfunction, triggering metabolic disorders, mitochondrial membrane potential collapse, and redox imbalance, ultimately leading to irreversible necrosis of tumor cells, thereby successfully achieving 'membrane necrotherapy'. This process simultaneously induces an immunogenic cell death (ICD)-like response, effectively promoting the dendritic cell maturation and the M1 polarization of macrophages, enhancing antitumor immune responses and suppressing distant metastasis. Importantly, the oxidative activity of BFO@Au NSs decays rapidly after reacting with tumor membranes, significantly reducing toxicity to biological tissues. This study proposes a new synergistic anti-tumor strategy based on membrane function disruption, providing a theoretical basis and application prospects for efficient and safe nanotherapeutic systems.