Bioengineered Bacterial Membrane Vesicles with Multifunctional Nanoparticles as a Versatile Platform for Cancer Immunotherapy.

Inducing immunogenic cell death (ICD) is a critical strategy for enhancing cancer immunotherapy. However, inefficient and risky ICD inducers along with a tumor hypoxia microenvironment seriously limit the immunotherapy efficacy. Non-specific delivery is also responsible for this inefficiency. In this work, we report a drug-free bacteria-derived outer membrane vesicle (OMV)-functionalized FeO-MnO (FMO) nanoplatform that realized neutrophil-mediated targeted delivery and photothermally enhanced cancer immunotherapy. In this system, modification of OMVs derived from enhanced the accumulation of FMO NPs at the tumor tissue through neutrophil-mediated targeted delivery. The FMO NPs underwent reactive decomposition in the tumor site, generating manganese and iron ions that induced ICD and O that regulated the tumor hypoxia environment. Moreover, OMVs are rich in pathogen-associated pattern molecules that can overcome the tumor immunosuppressive microenvironment and effectively activate immune cells, thereby enhancing specific immune responses. Photothermal therapy (PTT) caused by MnO and FeO can not only indirectly stimulate systemic immunity by directly destroying tumor cells but also promote the enrichment of neutrophil-equipped nanoparticles by enhancing the inflammatory response at the tumor site. Finally, the proposed multi-modal treatment system with targeted delivery capability realized effective tumor immunotherapy to prevent tumor growth and recurrence.