Lee Chaebin, Liu Xiangji, Zhang Weizhong, Duncan Michael A, Jiang Fangchao, Kim Christine, Yan Xuefeng, Teng Yong, Wang Hui, Jiang Wen, Li Zibo, Xie Jin
Department of Chemistry, University of Georgia, 140 Cedar Street, Athens, GA 30602, USA.
Nanoscale. 2021 May 28;13(20):9252-9263. doi: 10.1039/d0nr08166c. Epub 2021 May 13.
High-Z nanoparticles (HZNPs) afford high cross-section for high energy radiation and have attracted wide attention as a novel type of radiosensitizer. However, conventional HZNPs are often associated with issues such as heavy metal toxicity, suboptimal pharmacokinetics, and low cellular uptake. Herein, we explore gadolinium-intercalated carbon dots (Gd@Cdots) as a dose-modifying agent for radiotherapy. Gd@Cdots are synthesized through a hydrothermal reaction with an ultrasmall size (∼3 nm) and a high Gd content. Gd@Cdots can significantly increase hydroxyl radical production under X-ray irradiation; this is attributed to not only the photoelectric effects of Gd, but also the surface catalytic effects of carbon. Because carbon is biologically and chemically inert, Gd@Cdots show low Gd leakage and minimal toxicity. In vitro studies confirm that Gd@Cdots can efficiently enhance radiation-induced cellular damage, causing elevated double strand breaks, lipid peroxidation, and mitochondrial depolarization. When tested in mice bearing non-small cell lung cancer H1299 tumors, intravenously injected Gd@Cdots plus radiation leads to improved tumor suppression and animal survival relative to radiation alone while causing no detectable toxicity. Our studies suggest a great potential of Gd@Cdots as a safe and efficient radiosensitizer.
高原子序数纳米颗粒（HZNPs）对高能辐射具有高截面，作为一种新型放射增敏剂已引起广泛关注。然而，传统的HZNPs常常伴随着重金属毒性、药代动力学欠佳以及细胞摄取率低等问题。在此，我们探索钆插层碳点（Gd@Cdots）作为放射治疗的剂量修饰剂。Gd@Cdots通过水热反应合成，尺寸超小（约3纳米）且钆含量高。Gd@Cdots在X射线照射下可显著增加羟基自由基的产生；这不仅归因于钆的光电效应，还归因于碳的表面催化效应。由于碳在生物学和化学上是惰性的，Gd@Cdots表现出低钆泄漏和最小毒性。体外研究证实，Gd@Cdots可有效增强辐射诱导的细胞损伤，导致双链断裂增加、脂质过氧化和线粒体去极化。在携带非小细胞肺癌H1299肿瘤的小鼠中进行测试时，静脉注射Gd@Cdots加辐射相对于单独辐射可提高肿瘤抑制率和动物存活率，同时未产生可检测到的毒性。我们的研究表明，Gd@Cdots作为一种安全有效的放射增敏剂具有巨大潜力。
