双光子荧光影像技术在药物研发中的应用前景.PDFVIP

双光子荧光影像技术在药物研发中的应用前景  * 马军，田玉顺(延边大学药学院，吉林 延吉 133002) 摘要：双光子荧光显微成像技术具有高分辨率和高灵敏度，与激光共聚焦显微镜相比，它在成像的穿透深度上有显著提 高，大大降低光毒性和光漂白，这些优点有利于双光子荧光显微成像技术用于组织样品的候选药物筛选，有望成为有效 缩短新药研发周期、降低新药开发成本和提高新药命中率的手段。 关键词：双光子荧光影像；药物研发；双光子荧光探针；活影像 中图分类号：R96 文献标志码：A 文章编号：1007-7693(2016)03-0381-05 DOI: 10.13748/ki.issn1007-7693.2016.03.030 Application Prospect of Two-photon Flurescence Imaging Technology in Drug Development * MA Jun, TIAN Yushun (College of Pharmcy, Yanbian University, Yanji 133002, China) ABSTRACT: Two-photon fluorescence imaging system is a technique with high resolution and high sensitivity. By two-photon microscopy, the imaging depth of intact sectioning is improved greatly and the phototoxicity and photobleaching level are significantly decreased compare to confocal microscopy. The imaging system therefore have the potential to enhance our understanding of drug activity in live tissues during drug screening, which could aid decision to select drug candidates. It is hopeful to be a way for drug development with effectively shorten the new drug development cycle, reduction in the drug development cost and increase success ratio of new drugs. KEY WORDS: two-photon fluorescence imaging; drug development; two-photon fluorescence probe; live imaging 随着生活节奏的加快和生活环境的不断恶 化，频繁出现很多前所未闻的新疾病，因此需要 不断研发新药物。药物研发是一个长周期、高投 入、高风险的工作。在通常情况下，从发现先导 化合物到新药正式上市需要约 10 年时间，费用需 要数千万美元甚至上亿美元[1] 。不仅如此，传统药 图 1 单光子与双光子荧光探针产生荧光的原理 物发现方法的低效导致高资金投入的候选药物最 OP单光子荧光探针；TP双光子荧光探针；MP多光子荧光探针； hv光子；hvF荧光。 后在临床晚期试验中以失败告终的情况时常发 Fig. 1 Principles of one- and two-photon fluorescent probe 生，淘汰率很高，所以药物活性筛选方法很重要。