Platelet membrane-camouflaged Fe-PDAP nanozymes for synergistic photodynamic therapy and immune microenvironment remodeling in breast cancer.

Abstract

Photodynamic therapy (PDT) is a photosensitizer-based targeted therapeutic approach that has been widely explored in tumor therapy. Nevertheless, the hypoxic features and immunosuppressive status of the tumor microenvironment (TME) can severely limit the therapeutic efficacy of PDT. To address this critical bottleneck, this study constructed a multifunctional biomimetic nanoprobe to enhance PDT efficacy by synergistically alleviating hypoxia and regulating the TME. Using Fe-doped polydiaminopyridine (Fe-PDAP) nanozymes as carriers, the photosensitizer indocyanine green (ICG) and immunomodulator rapamycin (RAPA) were encapsulated, and the nanoparticles were further coated with platelet membrane (PM) to obtain the Fe-PDAP-ICG-RAPA@PM biomimetic nanosystem. Platelet-membrane modification endows nanoparticles with favorable tumor-targeting capacity and effectively improves their accumulation efficiency in tumor tissues. Within the TME, Fe-PDAP works synergistically with ICG to mitigate hypoxia-related limitations of PDT. Meanwhile, RAPA can drive the polarization of immunosuppressive M2 tumor-associated macrophages (TAMs) toward the antitumor M1 phenotype, thereby efficiently remodeling the immunosuppressive microenvironment. In addition, this biomimetic nanosystem possesses dual-modal magnetic resonance/fluorescence imaging capability. In summary, this study establishes a multifunctional biomimetic nanoplatform integrating dual-modal imaging and synergistic therapy. It can serve as a potential combination therapeutic strategy for breast cancer and provide a reference for the optimized design of subsequent multifunctional nanotheranostic systems.