Macrophage Membrane-Engineered Biomimetic Nanoplatform Enables Immune Evasion and Immunomodulation for Enhanced Chemo-Photodynamic Therapy

Triple-negative breast cancer (TNBC) remains one of the most aggressive breast cancer subtypes with insufficient therapeutic opportunities and poor clinical outcomes. This challenge can be addressed to a great extent by immunotherapy, but its clinical efficacy is substantially limited by the immunosuppressive tumor microenvironment. To overcome these barriers, an intelligent M1-type macrophage membrane camouflaged biomimetic nanoplatform based on cholesterol-functionalized glycopolymers bearing a photodynamic therapy (PDT)-active unit protoporphyrin IX (PpIX) and pH-responsive linkages for doxorubicin (Dox) conjugation has been developed to suppress TNBC through the combination of chemo-photodynamic therapy and immune remodeling. The therapeutic efficacy of the NP-Dox@M1 nanoplatform against metastatic TNBC was systematically evaluated in vitro through a comparative analysis of membrane-coated (NP@M1) versus uncoated (NP) constructs and drug-loaded (NP-Dox) versus drug-free formulations under conditions with or without light irradiation. The NP-Dox@M1 nanoplatform enables the synergistic combination of enhanced chemo-photodynamic therapy and immune regulation by promoting the polarization of macrophages toward an M1-like phenotype and reducing macrophage uptake, demonstrating potential immune evasion for the effective treatment of TNBC.