同位素标记有机碲探针以细胞分辨率揭示体内动态缺氧。
Isotopologous Organotellurium Probes Reveal Dynamic Hypoxia In Vivo with Cellular Resolution.
机构信息
Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6, Canada.
Departments of Radiation Oncology, Medical Biophysics, and the, STTARR Innovaton Centre, Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, Ontario, M5G 1L7, Canada.
出版信息
Angew Chem Int Ed Engl. 2016 Oct 10;55(42):13159-13163. doi: 10.1002/anie.201607483.
Changes in the oxygenation state of microenvironments within solid tumors are associated with the development of aggressive cancer phenotypes. Factors that influence cellular hypoxia have been characterized; however, methods for measuring the dynamics of oxygenation at a cellular level in vivo have been elusive. We report a series of tellurium-containing isotopologous probes for cellular hypoxia compatible with mass cytometry (MC)-technology that allows for highly parametric interrogation of single cells based on atomic mass spectrometry. Sequential labeling with the isotopologous probes (SLIP) in pancreatic tumor xenograft models revealed changes in cellular oxygenation over time which correlated with the distance from vasculature, the proliferation of cell populations, and proximity to necrosis. SLIP allows for capture of spatial and temporal dynamics in vivo using enzyme activated probes.
肿瘤微环境中的氧合状态的变化与侵袭性癌症表型的发展有关。已经描述了影响细胞缺氧的因素；然而，在体内测量细胞水平氧合动力学的方法一直难以捉摸。我们报告了一系列与质谱流式细胞术（MC）技术兼容的含碲同位素探针，用于细胞缺氧，该技术允许基于原子质谱对单个细胞进行高度参数化检测。在胰腺肿瘤异种移植模型中，用同位素探针进行连续标记（SLIP）揭示了细胞氧合随时间的变化，这些变化与距离血管、细胞群体的增殖以及与坏死的接近程度有关。SLIP 允许使用酶激活探针在体内捕获空间和时间动态。
Zotero 插件