Platelet backpacking nanoparticles based on bacterial outer membrane vesicles enhanced photothermal-immune anti-tumor therapy†

Abstract

Bacterial outer membrane vesicles (OMVs), produced by Gram-negative bacteria, retain the immunostimulatory capacity of parental bacteria. OMVs have been recognized as potent natural immune adjuvants and drug delivery vehicles. Photothermal therapy that triggers immunogenic cell death further stimulates the immune system by releasing damage-associated molecular patterns. This therapeutic effect can be synergized with OMVs to achieve enhanced anti-tumor outcomes. We also observed that tumors can recruit platelets. Leveraging the phenomenon, we have innovatively employed platelets as “couriers” to boost the tumor-targeting delivery efficiency of both OMVs and photothermal agents. In detail, based on OMVs, we meticulously engineered nanoparticles (IR780-SLN@O–P) with platelet-binding capacity. These “courier” platelets carry “cargo” IR780-SLN@O–P NPs to tumor sites via P-selectin, ensuring targeted delivery. Under laser irradiation, the photothermal agents generate significant photothermal effects, which combined with the immune-stimulating properties of OMVs, creating a robust anti-tumor immune response. For “cold” tumors such as triple-negative breast cancer (TNBC), our IR780-SLN@O–P NPs not only prolonged the survival of mice bearing 4T1 orthotopic tumors, but also significantly suppressed tumor growth. Moreover, they facilitated dendritic cell maturation and the infiltration of CD8⁺ T cells to ameliorate the immunosuppressive tumor environment. Our research aims to highlight the unique advantages of OMVs and explore the potential of the tumor-targeting strategy that synergizes photothermal therapy with immunotherapy. We hope that our findings can offer insights into TNBC clinical treatments.