Xiang Huandong, Li Xin, Wei Haoran, Zu Xu, Wan Yilong, Cheng Zan, Mao Tianjiao, Xiao Yu, Ren Genxing, Lu Jinyang, Fan Ping, Yuan Hui, Xiong Menghua, Meng Huan, Yan Liang, Zhao Yuliang
School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, 511442, P. R. China.
CAS Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, P. R. China.
Adv Mater. 2025 Aug;37(34):e2501077. doi: 10.1002/adma.202501077. Epub 2025 Jun 18.
Over the past 120 years, significant efforts are dedicated to delivering maximum radiation doses to tumor sites while sparing adjacent normal tissues as much as possible. Despite encouraging progress in the development of heavy metal-based nanoscale radiosensitizers, radiotherapy often fails to fully eradicate hypoxic tumors, leading to local recurrence or even progression to distant metastasis. In this study, a versatile biomimetic hybrid radiosensitizer is engineered by integrating the hypoxia-activated prodrug banoxantrone and CeO nanozymes into mesoporous silica-coated BiO nanoparticles (NPs), followed by camouflage coating with cancer-cell-derived membranes. Compared to naked BiO NPs and free banoxantrone alone, the radiosensitization efficacy of the biomimetic NPs is substantially enhanced toward both normoxic and hypoxic cancer cells. Moreover, lung metastasis is markedly inhibited by reactive oxygen species-mediated remodeling of the extracellular matrix through the activity of CeO nanozymes. As confirmed by in vitro and in vivo results, the biomimetic hybrid radiosensitizer enhances radiotherapy against lung metastasis with fewer side effects. This study provides compelling evidence for the development of next-generation radiosensitizers with optimized functionalities using biomimetic hybrid engineering to finely balance the benefits and risks of radiotherapy.
在过去的120年里，人们付出了巨大努力，致力于在尽可能保护邻近正常组织的同时，向肿瘤部位输送最大辐射剂量。尽管基于重金属的纳米级放射增敏剂的研发取得了令人鼓舞的进展，但放射治疗往往无法完全根除缺氧肿瘤，导致局部复发甚至进展为远处转移。在本研究中，通过将缺氧激活前药巴诺蒽醌和CeO纳米酶整合到介孔二氧化硅包覆的BiO纳米颗粒（NPs）中，然后用癌细胞衍生膜进行伪装包覆，构建了一种多功能仿生混合放射增敏剂。与裸BiO NPs和游离巴诺蒽醌相比，仿生NPs对常氧和缺氧癌细胞的放射增敏效果均显著增强。此外，CeO纳米酶的活性通过活性氧介导的细胞外基质重塑显著抑制了肺转移。体外和体内结果证实，这种仿生混合放射增敏剂以较少的副作用增强了对肺转移的放射治疗效果。本研究为利用仿生混合工程开发具有优化功能的下一代放射增敏剂提供了有力证据，以精细平衡放射治疗的益处和风险。
