College of Civil Engineering and Architecture , Shandong University of Science and Technology , Qingdao 266590 , China.
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics , Chinese Academy of Sciences , Beijing 100049 , China.
ACS Appl Mater Interfaces. 2019 May 29;11(21):18942-18952. doi: 10.1021/acsami.9b03636. Epub 2019 May 15.
The radioresistance of tumor cells is considered to be an Achilles' heel of cancer radiotherapy. Thus, an effective and biosafe radiosensitizer is highly desired but hitherto remains a big challenge. With the rapid progress of nanomedicine, multifunctional inorganic nanoradiosensitizers offer a new route to overcome the radioresistance and enhance the efficacy of radiotherapy. Herein, poly(vinylpyrrolidone) (PVP)-modified BiWO nanoplates with good biocompatibility were synthesized through a simple hydrothermal process and applied as a radiosensitizer for the enhancement of radiotherapy for the first time. On the one hand, the high- Z elements Bi ( Z = 83) and W ( Z = 74) endow PVP-BiWO with better X-ray energy deposition performance and thus enhance radiation-induced DNA damages. On the other hand, BiWO semiconductors exhibit significant photocurrent and photocatalytic-like radiocatalytic activity under X-ray irradiation, giving rise to the effective separation of electron/hole (e/h) pairs and subsequently promoting the generation of cytotoxic reactive oxygen species, especially hydroxyl radicals (OH). The γ-H2AX and clonogenic assays demonstrated that PVP-BiWO could efficiently increase cellular DNA damages and colony formations under X-ray irradiation. These versatile features endowed PVP-BiWO nanoplates with enhanced radiotherapy efficacy in animal models. In addition, BiWO nanoplates can also serve as good X-ray computed tomography imaging contrast agents. Our findings provide an alternative nanotechnology strategy for tumor radiosensitization through simultaneous radiation energy deposition and radiocatalysis.
肿瘤细胞的放射抗性被认为是癌症放射治疗的阿喀琉斯之踵。因此，人们非常希望有一种有效且生物安全的放射增敏剂，但迄今为止这仍然是一个巨大的挑战。随着纳米医学的快速发展，多功能无机纳米放射增敏剂为克服放射抗性和提高放射治疗效果提供了新途径。在此，通过简单的水热法合成了具有良好生物相容性的聚（聚乙烯吡咯烷酮）（PVP）修饰的 BiWO 纳米板，并首次将其用作放射增敏剂来增强放射治疗。一方面，高 Z 元素 Bi（Z=83）和 W（Z=74）使 PVP-BiWO 具有更好的 X 射线能量沉积性能，从而增强了辐射诱导的 DNA 损伤。另一方面，BiWO 半导体在 X 射线照射下表现出显著的光电流和类光催化辐射催化活性，导致电子/空穴（e/h）对的有效分离，并随后促进细胞毒性活性氧物种，特别是羟基自由基（OH）的生成。γ-H2AX 和集落形成实验表明，PVP-BiWO 可以在 X 射线照射下有效地增加细胞内 DNA 损伤和集落形成。这些多功能特性使 PVP-BiWO 纳米板在动物模型中具有增强的放射治疗效果。此外，BiWO 纳米板还可以用作良好的 X 射线计算机断层扫描成像造影剂。我们的研究结果为通过同时进行辐射能量沉积和辐射催化来实现肿瘤放射增敏提供了一种替代的纳米技术策略。
