Enhancing Radiotherapy for Hypoxic Tumors: Integrative Strategies Using Bacteria and Nanoparticles

Cancer remains a major global health challenge, with radiotherapy (RT) being a cornerstone of treatment. However, the efficacy of RT is significantly hindered by hypoxic tumor microenvironments (TMEs) and nonselective toxicity to healthy tissues. Recent advancements in combining bacteria and nanoparticles have shown promise in addressing these limitations. Cyanobacteria, with their oxygen-producing capabilities, alleviate tumor hypoxia, while anaerobic bacteria selectively target hypoxic regions. Nanoparticles complement these approaches by enhancing bacterial localization and amplifying radiosensitization through reactive oxygen species (ROS) generation and other synergistic therapies. Unlike previous reviews that have mainly focused on either bacterial therapy or nanoparticle-assisted radiosensitization separately, this review provides a comparative and integrative perspective on their combined use, emphasizing the novelty of synergistic strategies. This review explores innovative bacterial-nanoparticle integrations, highlighting their roles in overcoming hypoxia and improving RT outcomes. The potential of these strategies to transform cancer treatment is discussed, alongside challenges and future directions.