Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, United States of America. Severance Biomedical Science Institute, Yonsei University of College of Medicine, Seoul, 03722, Republic of Korea.
Nanotechnology. 2018 Dec 14;29(50):504001. doi: 10.1088/1361-6528/aae272. Epub 2018 Sep 19.
Gold nanoparticles (AuNPs) are known to sensitize cancer cells to radiation therapy (RT) by increasing the deposition of ionizing energy in their immediate vicinity. However, this process of dose enhancement is challenging to monitor because it is heterogeneous at the sub-cellular scale. Furthermore, radiation damage is primarily mediated by reactive oxygen species (ROS) that are produced following water radiolysis. Here, radiation-responsive PEGylated gold nanoparticles (RPAuNPs) were synthesized for the enhanced generation and concurrent detection of ROS in cancer cells and tumors. PEGylated gold particles (20 nm diameter) were functionalized with dihydrorhodamine 123 (DHR-123), a known ROS sensor, to monitor ROS generation in their immediate vicinity. These NPs were able to effectively radiosensitize cells, as measured by increased cell apoptosis following RT. Furthermore, the fluorescence of these RPAuNPs was 7-fold higher after 6 Gy RT due to the local production of ROS near the surface of the NP. Finally, multispectral fluorescence imaging was used to monitor NP-induced ROS in vivo, following conformal RT, in a xenograft model of breast cancer. This theranostic NP system provides a novel approach for monitoring the nanoscale enhancement of RT by high-Z metal NPs.
金纳米颗粒（AuNPs）通过增加其附近离子化能量的沉积，被认为可以使癌细胞对放射疗法（RT）敏感。然而，由于亚细胞尺度上的异质性，这种剂量增强过程难以监测。此外，辐射损伤主要是由水辐射分解后产生的活性氧物种（ROS）介导的。在这里，合成了辐射响应性聚乙二醇化金纳米颗粒（RPAuNPs），用于增强癌细胞和肿瘤中 ROS 的产生和同时检测。用二氢罗丹明 123（DHR-123）功能化聚乙二醇化金颗粒（20nm 直径），DHR-123 是一种已知的 ROS 传感器，用于监测其附近的 ROS 产生。这些 NPs 能够有效地放射增敏细胞，如 RT 后细胞凋亡增加所测量的那样。此外，由于 NP 表面附近产生的 ROS，这些 RPAuNPs 的荧光在 6Gy RT 后增加了 7 倍。最后，在乳腺癌异种移植模型中，使用多光谱荧光成像在顺形 RT 后监测体内 NP 诱导的 ROS。这种治疗诊断性 NP 系统为监测高 Z 金属 NPs 对 RT 的纳米尺度增强提供了一种新方法。
