为了解决放射治疗（RT）中由于肿瘤缺氧加剧和放射增敏剂的不均匀分布而导致的活性氧（ROS）产生不理想的问题。在这项工作中，一种新型纳米药物被命名为PLGA@IR780-Bi- DTPA (PIBD) 是通过将辐射敏化剂 Bi-DTPA 和光热剂 IR780 负载到聚乳酸-乙醇酸 (PLGA) 上而设计的。该设计利用 IR780 的肿瘤靶向能力，确保纳米粒子在肿瘤细胞中选择性积累，特别是在线粒体内。还检查了光热疗法增强放射治疗的效果，以评估缺氧的缓解和放射敏感性的增强。PIBD纳米颗粒表现出强大的线粒体靶向和选择性肿瘤积累能力。经808 nm激光照射激活后，纳米颗粒通过光热效应增强血液供应，提高氧含量，有效缓解局部缺氧，从而提高ROS的产生，实现有效的RT。比较研究表明，PIBD诱导的放疗在治疗缺氧肿瘤方面明显优于传统放疗。这种肿瘤靶向光热治疗增强放射治疗纳米药物的设计将推动靶向药物输送系统的开发，无论缺氧微环境如何，都能实现有效的放疗。© 2024 张等人。

To address the problem of suboptimal reactive oxygen species (ROS) production in Radiation therapy (RT) which was resulted from exacerbated tumor hypoxia and the heterogeneous distribution of radiation sensitizers.In this work, a novel nanomedicine, designated as PLGA@IR780-Bi-DTPA (PIBD), was engineered by loading the radiation sensitizer Bi-DTPA and the photothermal agent IR780 onto poly(lactic-co-glycolic acid) (PLGA). This design leverages the tumor-targeting ability of IR780 to ensure selective accumulation of the nanoparticles in tumor cells, particularly within the mitochondria. The effect of the photothermal therapy-enhanced radiation therapy was also examined to assess the alleviation of hypoxia and the enhancement of radiation sensitivity.The PIBD nanoparticles exhibited strong capacity in mitochondrial targeting and selective tumor accumulation. Upon activation by 808 nm laser irradiation, the nanoparticles effectively alleviated local hypoxia by photothermal effect enhanced blood supplying to improve oxygen content, thereby enhancing the ROS production for effective RT. Comparative studies revealed that PIBD-induced RT significantly outperformed conventional RT in treating hypoxic tumors.This design of tumor-targeting photothermal therapy-enhanced radiation therapy nanomedicine would advance the development of targeted drug delivery system for effective RT regardless of hypoxic microenvironment.© 2024 Zhang et al.