CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety , Institute of High Energy Physics, Chinese Academy of Sciences , Beijing 100049 , China.
College of Materials Science and Optoelectronic Technology , University of Chinese Academy of Sciences , Beijing 100049 , China.
ACS Nano. 2019 May 28;13(5):5947-5958. doi: 10.1021/acsnano.9b01818. Epub 2019 Apr 15.
Despite the development of nanomaterials with high-Z elements for radiosensitizers, most of them suffer from their oxygen-dependent behavior in hypoxic tumor, nonideal selectivity to tumor, or inevasible damages to normal tissue, greatly limiting their further applications. Herein, we develop a Schottky-type heterostructure of Au-BiS with promising ability of reactive free radicals generation under X-ray irradiation for selectively enhancing radiotherapeutic efficacy by catalyzing intracellular HO in tumor. On the one hand, like many other nanomaterials with rich high-Z elements, Au-BiS can deposit higher radiation dose within tumors in the form of high energy electrons. On the other hand, Au-BiS can remarkably improve the utilization of a large number of X-ray-induced low energy electrons during radiotherapy for nonoxygen dependent free radicals generation even in hypoxic condition. This feature of Schottky-type heterostructures Au-BiS attributes to the generated Schottky barrier between metal Au and semiconductor BiS, which can trap the X-ray-generated electrons and transfer them to Au, resulting in efficient separation of the electron-hole pairs. Then, because of the matched potential between the conduction band of BiS and overexpressed HO within tumor, the Au-BiS HNSCs can decompose the intracellular HO into highly toxic OH for selective radiosensitization in tumor. As a consequence, this kind of nanoparticle provides an idea to develop rational designed Schottky-type heterostructures as efficient radiosensitizers for enhanced radiotherapy of cancer.
尽管已经开发出了具有高 Z 元素的纳米材料作为放射增敏剂,但它们大多数都存在氧依赖性行为、非理想的肿瘤选择性或不可避免的正常组织损伤,这极大地限制了它们的进一步应用。在此,我们开发了一种 Au-BiS 的肖特基型异质结构,具有在 X 射线照射下生成反应性自由基的能力,可通过催化肿瘤内的 HO 来选择性地增强放射治疗效果。一方面,像许多其他富含高 Z 元素的纳米材料一样,Au-BiS 可以以高能电子的形式在肿瘤内沉积更高的辐射剂量。另一方面,Au-BiS 可以显著提高放疗过程中大量 X 射线诱导的低能电子的利用效率,从而即使在缺氧条件下也能生成非氧依赖的自由基。Au-BiS 肖特基型异质结构的这一特性归因于金属 Au 和半导体 BiS 之间产生的肖特基势垒,它可以捕获 X 射线产生的电子,并将其转移到 Au 上,从而实现电子-空穴对的有效分离。然后,由于 BiS 的导带和肿瘤内过表达的 HO 之间的匹配电位,Au-BiS HNSCs 可以将细胞内的 HO 分解为高毒性的 OH,从而实现肿瘤的选择性放射增敏。因此,这种纳米颗粒为开发合理设计的肖特基型异质结构作为增强癌症放射治疗的高效放射增敏剂提供了一种思路。