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 Fe3O4-MnO2 (FMO) nanoplatform that realized neutrophil-mediated
targeted delivery and photothermally enhanced cancer immunotherapy.
In this system, modification of OMVs derived from Escherichia
coli 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 O2 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 MnO2 and Fe3O4 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.
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