Bimetallic nanozymes with galvanic cell effects eradicate intratumoral bacteria and tumor cells to overcome drug resistance and potentiate antitumor immune responses for tumor therapy.

Abstract

Intratumoral bacteria have attracted considerable attention as critical components of the tumor microenvironment (TME) that influence tumor initiation, progression, therapeutic efficacy, and immune responses. Conventional antibiotic approaches for eradicating intratumoral bacteria are limited by severe side effects, disruption of microbial homeostasis, and the emergence of multidrug resistance, while offering no direct tumoricidal effects. Here, we developed bimetallic Copper-Tin nanozymes (CuSn nanozymes) with a galvanic cell effect to overcome bacteria-associated challenges, overcome drug resistance, and enhance cancer therapy. The nanozymes can generate highly active electrons and metal ions at tumor sites without external stimulation, achieving massive reactive oxygen species (ROS) production and effective tumor eradication. The released electrons disrupt bacterial electron transport chains (ETC), thereby inhibiting energy synthesis and achieving potent antibacterial effects. The release of copper ions further enhances ROS-mediated antibacterial activity. Moreover, bacterial eradication promotes antitumor immune activation, further enhancing therapeutic outcomes. Using breast, endometrial, and liver cancer models, we demonstrated the broad applicability of this approach. This work not only offers a new paradigm for designing innovative bimetallic nanozymes with enhanced catalytic activity but also provides a potential therapeutic approach for simultaneously eliminating bacteria and tumors, overcoming chemoresistance, and offering effective treatment without reliance on conventional antibiotics or chemotherapeutics for microbiota-enriched tumors.