Chai Rong, Yu Luodan, Dong Caihong, Yin Yipengchen, Wang Sheng, Chen Yu, Zhang Qin
Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, PR China.
Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, PR China.
Bioact Mater. 2022 Jan 20;17:276-288. doi: 10.1016/j.bioactmat.2022.01.014. eCollection 2022 Nov.
The local hypoxic tumor environment substantially hampers the therapeutic efficiency of radiotherapy, which typically requires the large X-ray doses for tumor treatment but induces the serious side effects. Herein, a biomimetic radiosensitized platform based on a natural oxygen-evolving photosynthetic cyanobacteria combined with two-dimensional (2D) bismuthene with high atomic-number (Z) components, is designed and engineered to effectively modulate the radiotherapy-resistant hypoxic tumor environment and achieve sufficient radiation energy deposition into tumor. Upon the exogenous sequential irradiation of 660 nm laser and X-ray beam, continuous photosynthetic oxygen evolution by the cyanobacteria and considerable generation of reactive oxygen species by the 2D bismuthene radiosensitizer substantially augmented the therapeutic efficacy of radiotherapy and suppressed the tumor growth, as demonstrated on both LLC-lung tumor xenograft-bearing C57/B6 mice model and 4T1-breast tumor xenograft-bearing Balb/c mice model, further demonstrating the photosynthetic hypoxia-alleviation capability and radiosensitization performance of the engineered biomimetic radiosensitized platform. This work exemplifies a distinct paradigm on the construction of microorganism-enabled tumor-microenvironment modulation and nanoradiosensitizer-augmented radiotherapy for efficient tumor treatment.
局部缺氧的肿瘤微环境严重阻碍了放射治疗的疗效，放射治疗通常需要大剂量的X射线来治疗肿瘤，但会引发严重的副作用。在此，设计并构建了一种基于天然产氧光合蓝细菌与具有高原子序数（Z）成分的二维（2D）铋烯相结合的仿生放射增敏平台，以有效调节放疗抗性缺氧肿瘤微环境，并实现足够的辐射能量沉积到肿瘤中。在660 nm激光和X射线束的外源顺序照射下，蓝细菌持续进行光合放氧以及二维铋烯放射增敏剂大量产生活性氧，显著增强了放射治疗的疗效并抑制了肿瘤生长，这在携带LLC-肺癌肿瘤异种移植物的C57/B6小鼠模型和携带4T1-乳腺癌肿瘤异种移植物的Balb/c小鼠模型上均得到了证实，进一步证明了所构建的仿生放射增敏平台的光合缓解缺氧能力和放射增敏性能。这项工作例证了一种独特的范例，即构建基于微生物的肿瘤微环境调节和纳米放射增敏剂增强的放射治疗以实现高效肿瘤治疗。
