Dual-targeted bacterial outer membrane vesicles enhance glioblastoma immunotherapy by regulating tumor microenvironment and inducing IFN-γ-mediated ferroptosis.

ABSTRACT: Glioblastoma (GBM) immunotherapy is limited by the blood-brain barrier (BBB) and the tumor immune resistance. Here, we develop an engineered bacterial outer membrane vesicle (OMV) through safe and straightforward genetic modification of Escherichia coli, termed OMV-C-C, enabling co-expression of cell-penetrating peptides (CPP) and chlorotoxin (CLT) on its surface. The OMV-C-C efficiently crosses BBB and specifically targets tumor cells both in vitro and in vivo. A single intravenous administration of OMV-C-C significantly inhibit GBM growth by enhancing the infiltration of CD8⁺ T cells in orthotopic brain tumor models. Mechanistically, interferon-gamma (IFN-γ) released by CD8⁺ T cells induces ferroptosis-specific lipid peroxidation in tumor cells through inhibiting cy

SUBMITTER: Chen C 

PROVIDER: S-EPMC12817401 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature