Designing Bioinspired 2D MoSe2 Nanosheet for Efficient Photothermal-Triggered Cancer Immunotherapy with Reprogramming Tumor-Associated Macrophages

Nonspecific absorption and clearance of nanomaterials during circulation is the major cause for treatment failure in nanomedicine-based cancer therapy. Therefore, herein bioinspired red blood cell (RBC) membrane is employed to camouflage 2D MoSe2 nanosheets with high photothermal conversion efficiency to achieve enhanced hemocompatibility and circulation time by preventing macrophage phagocytosis. RBC MoSe2-potentiated photothermal therapy (PTT) demonstrates potent in vivo antitumor efficacy, which triggers the release of tumor-associated antigens to activate cytotoxic T lymphocytes and inactivate the PD-1/PD-L1 pathway to avoid immunologic escape. Furthermore, in the ablated tumor microenvironment, the tumor-associated macrophages are effectively reprogrammed to tumoricidal M1 phenotype to potentiate the antitumor action. Taken together, this biomimetic functionalization thus provides a substantial advance in personalized PTT-triggered immunotherapy for clinical translation.