Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University , Changchun 130021, China.
ACS Appl Mater Interfaces. 2014 Jul 23;6(14):11082-90. doi: 10.1021/am503998x. Epub 2014 Jul 8.
Exploring intracellular behavior of suicide gene is significant for improving the efficacy and safety of herpes simplex virus thymidine kinase gene/ganciclovir (HSV-TK/GCV) system in cancer therapy. Molecular imaging represents a powerful tool to understand gene transportation and function dynamics. In this work, we reported a quantum-dot-based technique for revealing the procedure of HSV-TK/GCV suicide gene therapy by constructing covalent linkage between near-infrared fluorescent quantum dots (QDs) and TK gene. This stable QD labeling did not influence either the QDs fluorescence or the biological activity of TK gene. Furthermore, we visualized and dynamically traced the intracellular behavior antitumor effect of TK gene in vitro and in vivo. It is demonstrated that TK gene was shuttled to the nucleus after a-24 h treatment; at that time the single dose of GCV administration exerts the gradually increasing lethal effect until to 72 h. Real-time tracing the formation of hepatocellular carcinoma treated with HSV-TK/GCV suicide gene system in vivo by QD-based NIR fluorescence imaging provides useful insight toward QD-based theranostics in future cancer therapy.
探索自杀基因的细胞内行为对于提高单纯疱疹病毒胸苷激酶基因/更昔洛韦（HSV-TK/GCV）系统在癌症治疗中的疗效和安全性具有重要意义。分子成像代表了一种了解基因运输和功能动态的强大工具。在这项工作中，我们通过构建近红外荧光量子点（QD）和 TK 基因之间的共价键，报道了一种基于量子点的技术来揭示 HSV-TK/GCV 自杀基因治疗的过程。这种稳定的 QD 标记既不影响 QD 的荧光，也不影响 TK 基因的生物学活性。此外，我们在体外和体内可视化和动态追踪了 TK 基因的抗肿瘤作用的细胞内行为。结果表明，TK 基因在处理 24 小时后被转运到细胞核；此时，单次给予 GCV 剂量会逐渐增加致死作用，直到 72 小时。通过基于 QD 的近红外荧光成像对体内 HSV-TK/GCV 自杀基因系统治疗的肝癌进行实时追踪，为未来癌症治疗中的 QD 治疗学提供了有用的见解。
