Department of Chemistry, Brock University, St. Catharines, Ontario, Canada.
Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada.
Bioorg Med Chem Lett. 2019 Jan 1;29(1):107-114. doi: 10.1016/j.bmcl.2018.10.052. Epub 2018 Nov 2.
The production and use of multi-modal imaging agents is on the rise. The vast majority of these imaging agents are limited to a single length scale for the agent (e.g. tissues only), which is typically at the organ or tissue scale. This work explores the synthesis of such an imaging agent and discusses the applications of our vitamin E-inspired multi-modal and multi-length scale imaging agents TB-Toc ((S,E)-5,5-difluoro-7-(2-(5-((6-hydroxy-2,5,7,8-tetramethylchroman-2-yl) methyl) thiophen-2-yl) vinyl)-9-methyl-5H-dipyrrolo-[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide). We investigate the toxicity of TB-Toc along with the starting materials and lipid based delivery vehicle in mouse myoblasts and fibroblasts. Further we investigate the uptake of TB-Toc delivered to cultured cells in both solvent and liposomes. TB-Toc has low toxicity, and no change in cell viability was observed up to concentrations of 10 mM. TB-Toc shows time-dependent cellular uptake that is complete in about 30 min. This work is the first step in demonstrating our vitamin E derivatives are viable multi-modal and length scale diagnostic tools.
多模态成像剂的生产和使用正在兴起。这些成像剂绝大多数仅限于单一的尺度（例如仅组织），通常在器官或组织尺度上。本工作探索了此类成像剂的合成，并讨论了我们受维生素 E 启发的多模态和多长度尺度成像剂 TB-Toc（(S,E)-5,5-二氟-7-(2-(5-((6-羟基-2,5,7,8-四甲基色满-2-基)甲基)噻吩-2-基)乙烯基)-9-甲基-5H-二吡咯并[1,2-c:2',1'-f][1,3,2]二氮杂硼烷-4-ium-5-ide）的应用。我们研究了 TB-Toc 及其起始材料和基于脂质的递药载体在小鼠成肌细胞和纤维母细胞中的毒性。此外，我们还研究了 TB-Toc 在溶剂和脂质体中递送到培养细胞中的摄取情况。TB-Toc 的毒性较低，在高达 10mM 的浓度下，观察到细胞活力没有变化。TB-Toc 显示出时间依赖性的细胞摄取，约 30 分钟即可完全摄取。这项工作是证明我们的维生素 E 衍生物是可行的多模态和长度尺度诊断工具的第一步。
