Magnetic Persistent Luminescence Nanoparticles Repolarize Tumor-Associated Macrophages for Enhanced Cancer Immunotherapy

M2-like tumor-associated macrophages (M2-TAMs) are key factors in creating an immunosuppressive tumor microenvironment (TME). Transforming M2-TAMs to immunostimulatory M1-TAMs is essential to reverse the immunosuppressive state of the TME. Herein, we develop a TAM nanopolarization regulator (mZ@ZFR@CM) by loading persistent luminescence nanoparticles, magnetic nanoparticles ZnFe 2 O 4 and R848 in mesoporous silica while wrapping tumor cell membrane, which efficiently converts M2-TAMs to M1-TAMs. We first discovered that ZnFe 2 O 4 has excellent M2-TAM repolarization capability. Furthermore, high-sensitivity persistent luminescence imaging confirms the efficient accumulation of mZ@ZFR@CM in tumor, significantly improving M2-TAM repolarization efficiency. In vivo assays demonstrate that mZ@ZFR@CM induces efficient repolarization of M2-TAMs and successfully reverses the immunosuppressive TME. Assisted by anti-PD-L1, mZ@ZFR@CM triggers a potent antitumor immune response, significantly inhibits tumor growth, and further initiates a specific antitumor immune memory response, providing protection against tumor recurrence and metastasis. This study demonstrates an efficient nanopolarization regulator of TAMs to reverse the immunosuppressive TME.