Bismuth-functionalized probiotics for enhanced antitumor radiotherapy and immune activation†

Radiotherapy (RT) is a mainstay treatment modality for solid tumors, employing high-energy radiation to induce reactive oxygen species (ROS) generation and DNA damage. However, RT is limited by insufficient DNA damage and collateral damage to normal tissues. Developing next-generation nanoradio-sensitizers to enhance tumor radiosensitivity while sparing healthy tissues remains a significant challenge. Herein, We propose a versatile bio–nano hybrid therapeutic system (BPBR), comprising Bifidobacterium infantis, bismuth-based nanoparticles, and the toll-like receptor 7/8 agonist (Resiquimod, R848). B. infantis exhibits tumor hypoxia-targeting properties, enabling the targeted delivery of bismuth nanoparticles and R848 to the tumor site. Bismuth, a high-atomic-number metal, possesses a higher mass attenuation coefficient for X-rays, enhancing X-ray radiation energy deposition and inducing DNA damage. R848, an activator of toll-like receptor 7/8, triggers immune responses. The combination of BPBR and X-ray irradiation significantly suppressed tumor growth in mice. This versatile bio–nano hybrid therapeutic system holds considerable promise for clinical translation and provides valuable insights for the design and development of novel therapeutics.