开发有效的方法来增强肿瘤的放射敏感性对于提高放射治疗（RT）的疗效至关重要。由于其深层组织穿透性、优异的安全性和精确的可控性，基于声敏剂的声动力疗法（SDT）作为一种有前途的与 RT 相结合的方法，最近受到了广泛的关注。然而，其活性氧（ROS）生成能力有限。声敏剂的聚集状态和缺乏特定的细胞器靶向阻碍了它们增强 RT 的潜力。这项研究介绍了指导聚集状态下使用的高性能声敏剂设计的基本原理。基于这些原理，我们通过有机合成开发了一种具有聚集诱导发射（AIE）特性的线粒体靶向声敏剂分子（TCSVP）。然后，我们使用共焦激光扫描显微镜 (CLSM) 和荧光显微镜证明了 TCSVP 在超声下在 H460 癌细胞中靶向线粒体并产生 ROS 的能力。随后，我们在H460细胞以及H460和4T1荷瘤小鼠中检验了利用TCSVP和超声增强肿瘤放射敏感性的有效性。结果表明，超声刺激下TCSVP在肿瘤中诱发非致命性线粒体氧化应激可以显着改善肿瘤的放射敏感性。放射敏感性（p <0.05）。此外，TCSVP 的体内安全性得到了组织病理学分析的彻底证实。这项工作提出了设计高效声敏剂的策略，并强调引发非致命性线粒体氧化应激是增强肿瘤放射敏感性的有效方法。版权所有 © Bentham Science Publishers；如有任何疑问，请发送电子邮件至 epub@benthamscience.net。

Developing effective methods to enhance tumor radiosensitivity is crucial for improving the therapeutic efficacy of radiotherapy (RT). Due to its deep tissue penetration, excellent safety profile, and precise controllability, sonosensitizer- based sonodynamic therapy (SDT) has recently garnered significant attention as a promising combined approach with RT.However, the limited reactive oxygen species (ROS) generation ability in the aggregated state and the absence of specific organelle targeting in sonosensitizers hinder their potential to augment RT. This study introduces a fundamental principle guiding the design of high-performance sonosensitizers employed in the aggregated state. Building upon these principles, we develop a mitochondria-targeted sonosensitizer molecule (TCSVP) with aggregation-induced emission (AIE) characteristics by organic synthesis. Then, we demonstrate the abilities of TCSVP to target mitochondria and produce ROS under ultrasound in H460 cancer cells using confocal laser scanning microscopy (CLSM) and fluorescence microscopy. Subsequently, we examine the effectiveness of enhancing tumor radiosensitivity by utilizing TCSVP and ultrasound in both H460 cells and H460 and 4T1 tumor-bearing mice.The results indicate that evoking non-lethal mitochondrial oxidative stress in tumors by TCSVP under ultrasound stimulation can significantly improve tumor radiosensitivity (p <0.05). Additionally, the in vivo safety profile of TCSVP is thoroughly confirmed by histopathological analysis.This work proposes strategies for designing efficient sonosensitizers and underscores that evoking non-lethal mitochondrial oxidative stress is an effective method to enhance tumor radiosensitivity.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.