A Multicyclic Catalytic Network Enabling ROS Amplification, Metabolic Disruption, and Immune Modulation for Antitumor-Antibacterial Therapy.

Abstract

Intratumoral bacteria are increasingly recognized as important regulators of tumor progression, immune suppression, and metastasis, whereas current therapeutic strategies remain insufficient to address the coupled tumor-bacteria microenvironment. Here, we report a multicyclic catalytic network (VBC-Net) that integrates alkaline polyoxovanadate with a Bi2WO6-CuSx p-n heterojunction for coordinated antitumor-antibacterial immunotherapy. Unlike conventional single-mechanism nanozymes, VBC-Net establishes interconnected catalytic cycles that sustain ROS amplification, oxygen activation, and glutathione depletion, thereby converting transient catalytic activity into persistent oxidative stress. Simultaneously, the alkaline microenvironment and Bi-associated interference with respiratory-chain-related processes may contribute to metabolic perturbation, coupling oxidative stress with metabolic disruption. VBC-Net is further associated with dendritic-cell maturation, enhanced T-cell infiltration, and pro-inflammatory immune modulation, suggesting remodeling of the tumor-bacteria-immune microenvironment. In murine 4T1 tumor and MRSA-infected models, VBC-Net achieves pronounced tumor suppression, bacterial clearance, reduced metastatic progression, and accelerated wound healing with good biocompatibility. This work establishes a multicyclic catalytic strategy for targeting complex tumor-associated ecosystems and provides a promising framework for antitumor-antibacterial therapy.

Abstract as supplied by the indexing source. © the authors / publisher.