Biomimetic multifunctional nanoparticles for improved radiotherapy and immunotherapy in cancer treatment

Radiotherapy represents a conventional approach in clinical cancer treatment, but suffers from insufficient DNA damage and limited tumor selectivity. Herein, bismuth oxyiodide quantum dots loaded hollow manganese dioxide (MB) nanoparticles was fabricated and subsequently wrapped with bacterial membrane vesicles (MVs) to create MB@MV nanoparticles. This biomimetic radiosensitizer is designed to enhance the efficacy of radiotherapy through a combined approach of tumor immunotherapy and oxygen delivery strategy. Upon systemic administration, MB@MV enhance tumor accumulation through specifically targeting the inflammatory milieu mediated by MVs, thereby activating dendritic cell-mediated innate immunotherapy. Concurrently, MB@MV demonstrate superior X-ray absorption, leading to effective DNA damage in tumor cells due to the high atomic number of bismuth. Notably, manganese dioxide react with the overexpressed H₂O₂ in the tumor microenvironment to alleviate hypoxia and fixing X-ray induced DNA damage in tumor cells, culminating in a multi-strategy approach to enhance radiotherapy sensitization. The findings from both <i>in vitro</i> and <i>in vivo</i> experiments demonstrate a significantly enhanced inhibition of tumor growth by MB@MV compared to tumors treated solely with X-ray. Overall, our multifunctional radiosensitizer MB@MV shows considerable promise in the field of tumor radiotherapy.