Engineered macrophage-derived cellular vesicles for NIR-II fluorescence imaging-guided precise cancer photo-immunotherapy.

Significant progress has been made in cancer immunotherapy; however, challenges such as interpatient variability, limited treatment response, and severe side effects persist. Although nanoimmunotherapy has emerged as a promising approach, the construction of precise and efficient nanosystems remain formidable challenges. Herein, a multifunctional nanoplatform was developed using macrophage-derived cellular vesicles (MCVs) for NIR-II imaging-guided precise cancer photo-immunotherapy. MCVs exhibited excellent tumor targeting and TAMs re-education effects, serving as both delivery carriers and therapeutic agents. Through amide bond, indocyanine green (ICG) was conjugated to the surface of MCVs, enabling in vivo tracking of MCVs distribution. Notably, ICG exhibited dual functionality as a NIR-II fluorescent agent and possessed photodynamic and photothermal effects, enabling the conversion of light energy into chemical or heat energy to eliminate tumor cells. This precision phototherapy triggered immunogenic cell death (ICD) of tumor, thereby activating the anti-tumor immune response. Additionally, MCVs loaded with R848, a toll-like receptor agonist, augmented the ICD-induced anti-tumor immunity. Animal experiments confirmed that MCVs-mediated photoimmunotherapy promoted T cell infiltration, inhibited tumor growth, and improved survival rates. In conclusion, we have developed a promising precision immunotherapy strategy capable of enhancing the immune response while mitigating off-target effects. These findings offer encouraging prospects for clinical translation.