Engineered Bacteria for Enhanced Radiotherapy against Breast Carcinoma

Radiotherapy is widely applied for multiple malignant tumors ablation in the clinic. However, redundant doses of X-rays might destroy normal tissue in the periphery of tumor sites. Here, we developed an integrated nanosystem (Bac@BNP) composed of engineered bacteria (Bac) and Bi2S3 nanoparticles (BNPs) for sensitizing radiotherapy. Bac could target and colonize in tumor sites alternatively, which overexpressed cytolysin A (ClyA) protein to regulate the cell cycle from a radioresistant phase to a radiosensitive phase. Simultaneously, peptide-modified BNPs, as a radiosensitizer with a high-Z element, was released from the surface of Bac owing to the matrix metalloproteinase-2 (MMP-2) response in the tumor microenvironment. Under X-ray irradiation, BNPs could enhance the radiotherapy sensitivity by triggering the intracellular generation of reactive oxygen species (ROS), coupled with DNA damage. In this constructed nanosystem, the combination of Bac@BNP and X-ray irradiation led to significant suppression of breast carcinoma in murine models with reduced side effects.

Automated summary

In this study, an integrated nanosystem composed of engineered bacteria and nanoparticles was developed for sensitizing radiotherapy. The system could target tumor sites and release a radiosensitizer, enhancing the effectiveness of radiotherapy.