Biomimetic M1 Macrophage Membrane-Camouflaged Nanoplatform Remodels Tumor Microenvironment for Enhanced Antitumor Immunity

Purpose: Immunotherapy has attracted increasing attention in cancer treatment, but its efficacy is greatly limited due to the low immunogenicity of tumors and immunosuppressive tumor microenvironment (TME). To address this, we constructed a biomimetic M1 macrophage membrane-Camouflaged nanoplatform (M1@CTP) for the co-delivery of the natural antitumor compound Tanshinone IIA (Tan IIA) and the immunogenic cell death (ICD) inducer Copper-diethyldithiocarbamate (CuET) to enhance antitumor immunity. Methods: CuET/Tan IIA/PLGA (CTP) nanoparticles were synthesized using a previously reported two-step emulsification method. Subsequently, these nanoparticles were then coated with induced M1 macrophage membranes to obtain M1@CTP. We systematically characterized their morphology, physicochemical properties, and environmental stability. In vitro studies assessed cytotoxicity, immune activation, and tumor-targeting capability. Subsequently, the antitumor efficacy and modulation of the TME were assessed in vivo. Finally, the biosafety of the nanoplatform was evaluated via histopathological and biochemical analyses. Results: Endowed by M1 macrophage membran coating, M1@CTP enables immune evasion and tumor homing, thereby prolonging systemic circulation time and achieving efficient tumor accumulation. Our study demonstrates that M1@CTP synergistically induces potent ICD, promotes dendritic cell maturation, and remodels the TME, leading to the infiltration of cytotoxic T lymphocytes. This process effectively converts “cold” tumors into “hot” ones and elicits a robust systemic antitumor immune response with favorable safety profiles. In addition, M1@CTP significantly enhanced the efficacy of immune checkpoint inhibitors in cold tumor models. Conclusion: This study provides an innovative and precise immunotherapy nanoplatform that coordinately modulates the TME and induces robust antitumor immunity, offering a promising strategy to overcome current limitations in immunotherapy.