文章:
单细胞抗癌药物作用的成像
Imaging of anticancer drug action in single cells
原文发布日期:2017-06-23
DOI: 10.1038/nrc.2017.41
类型: Review Article
开放获取: 否
要点:
- The in vivo microscopy toolbox enables extended live-animal 3D imaging in orthotopic disease sites, deeper imaging through tissue and multiple simultaneous molecular measurements.
- Imaging of multiple single cells can assess tumour heterogeneity, tumour evolution following drug treatment and drug–target binding; it also enables visualization of micro-anatomical structures and distinct and rare cell types.
- Fluorescently labelled drugs and nanoformulations reveal mechanisms of delivery and binding within tumours.
- Imaging can show differences in drug response in vivo compared with in vitro tissue culture models.
- Components of the tumour microenvironment, including the extracellular matrix, immune cells and vasculature, can be studied for their role in influencing drug action.
- The distribution and effect of immunotherapies including those that block immune checkpoints can be visualized in the tumour and draining lymph nodes.
- In vivo microscopy provides a complementary high-resolution perspective to lower-resolution imaging modalities such as positron emission tomography–computed tomography and magnetic resonance imaging that are used in the clinic.
要点翻译:
- 活体显微技术工具包能够在原位疾病部位进行延长的活体动物三维成像,通过组织实现更深层成像,并同步进行多重分子测量。
- 多重单细胞成像可评估肿瘤异质性、药物治疗后的肿瘤演化及药物-靶点结合情况,同时还能实现微解剖结构以及独特和稀有细胞类型的可视化。
- 荧光标记药物和纳米制剂揭示了药物在肿瘤内的递送和结合机制。
- 成像技术能够显示体内药物反应与体外组织培养模型之间的差异。
- 肿瘤微环境的组成部分,包括细胞外基质、免疫细胞和血管系统,可被研究以了解其在影响药物作用中的角色。
- 免疫疗法(包括阻断免疫检查点的疗法)在肿瘤和引流淋巴结中的分布和效果可以实现可视化。
- 与临床使用的低分辨率成像模式(如正电子发射断层扫描-计算机断层扫描和磁共振成像)相比,活体显微镜技术提供了一种互补的高分辨率视角。
英文摘要:
Imaging is widely used in anticancer drug development, typically for whole-body tracking of labelled drugs to different organs or to assess drug efficacy through volumetric measurements. However, increasing attention has been drawn to pharmacology at the single-cell level. Diverse cell types, including cancer-associated immune cells, physicochemical features of the tumour microenvironment and heterogeneous cell behaviour all affect drug delivery, response and resistance. This Review summarizes developments in the imaging of in vivo anticancer drug action, with a focus on microscopy approaches at the single-cell level and translational lessons for the clinic.
摘要翻译:
影像学广泛应用于抗癌药物研发,通常用于追踪标记药物在全身的分布或评估疗效。然而,单细胞水平的药理学日益受到关注。不同细胞类型(如肿瘤相关免疫细胞)、肿瘤微环境的理化特征及细胞异质性均影响药物递送、疗效与耐药。本文综述了体内抗癌药物作用的影像学研究进展,重点介绍单细胞水平的显微技术及其临床转化启示。
原文链接:
Imaging of anticancer drug action in single cells