Bionic 'Trojan Horse' nanoparticles based on Fe-Cu bimetallic MOFs enhance anti-tumor immunotherapy through multimodal synergistic effects.

The therapeutic efficacy of cisplatin-based chemotherapy for lung cancer is often limited by low tumor specificity and off-target toxicity. To address these challenges, we have developed a biomimetic "Trojan horse" nanoparticle (RLMPt-NPs), inspired by the multifunctional properties of biological membranes. The nanoparticle consists of a cisplatin-loaded iron-copper metal-organic framework (MOF) core coated with a polymerized biomimetic platform derived from the fusion of erythrocyte and homologous lung cancer cell membranes. This design facilitates a programmed two-stage release mechanism. Initially, the rapid release of Fe/Cu ions depletes intracellular glutathione, priming tumor cells for treatment. Subsequently, cisplatin is sustainably released from the destabilized MOF, enhancing its chemotherapeutic efficacy. This synergistic approach amplifies the combined effects of chemodynamic therapy and chemotherapy, leading to significant tumor cell damage. This damage promotes the release of tumor-associated antigens, which in turn drives dendritic cell maturation and activates T-cell responses. When combined with anti-PD1 immunotherapy in a mouse lung cancer model, RLMPt-NPs induced a robust systemic antitumor immune response, effectively suppressing primary tumor growth and establishing long-term immune memory to prevent recurrence. By integrating biological camouflage, homologous targeting, chemodynamic therapy, and chemotherapy into a single nanoplatform, this design achieves synergistic coordination of multiple therapeutic mechanisms. This broadens the therapeutic window for chemo-immunotherapy, demonstrating significant potential for translation into multimodal cancer therapy.