Enhancing Tumor ROS Generation via Nanozyme-Amplified Photodynamic Therapy with Oxygen-Supplying Bacterial OMVs

Abstract

Bacterial outer membrane vesicles (OMVs) possess inherent tumor-accumulation capabilities, immunostimulatory potential, and a size-dependent enhanced permeability and retention (EPR) effect, making them promising carriers for cancer immunotherapy. In this study, a biomimetic nanoassembly, OMV@Hb-Ce6-Mn, was constructed by co-loading hemoglobin (Hb) and chlorin e6 (Ce6) onto OMVs, followed by modification with manganese dioxide (MnO2) nanoparticles. Within the tumor microenvironment, Mn ions were released from OMV@Hb-Ce6-Mn and catalyzed H2O2 to generate hydroxyl radicals (·OH) through Fenton-like reaction. Under laser irradiation, Ce6 generated singlet oxygen (1O2), while Hb enhanced local oxygen (O2), availability, synergistically amplifying reactive oxygen species (ROS) generation. The ROS induced immunogenic cell death in tumors, and under the action of OMVs, it further activated the immune response. In vivo, OMV@Hb-Ce6-Mn significantly suppressed tumor growth and elicited potent systemic antitumor immunity, achieving a 50-day survival rate of 83.3%, compared to complete mortality in control group by day 25. This strategy demonstrates the therapeutic potential of integrating microbial vesicle-based delivery with ROS-mediated tumor modulation for effective multimodal cancer therapy.