Ultrasound-responsive engineered bacteria mediated specific controlled expression of catalase and efficient radiotherapy.

The limited efficacy of radiotherapy (RT) in breast cancer is intricately linked to the hypoxic tumor microenvironment. Delivering catalase (CAT) to decompose hydrogen peroxide (HO) into oxygen is a promising strategy to address this. However, challenges such as low transport efficiency, accumulation in normal organs, and lack of spatiotemporal control hinder its clinical application. To address this, we developed an innovative ultrasound-responsive engineered bacteria-based CAT delivery system (UEB), which effectively overcomes these challenges by targeting tumors, ensuring efficient CAT expression, and providing precise spatiotemporal control over HO decomposition. When subjected to ultrasound irradiation, the decomposition of HO and the production of oxygen by UEB increased threefold, demonstrating excellent capability in alleviating hypoxia. CAT accumulation in normal organs was minimized through this ultrasound-responsive delivery strategy. Moreover, these engineered bacteria enhance reactive oxygen species (ROS) generation, improving RT outcomes and significantly inhibiting tumor growth, resulting in a 10-fold tumor size reduction. This study demonstrates a promising strategy for the specific, controlled expression of CAT by the application of ultrasound-responsive engineered bacteria to enhance the efficacy of tumor radiotherapy.