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.