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Single-cell analysis: visualizing pharmaceutical and metabolite uptake in cells with label-free 3D mass spectrometry imaging

机译:单细胞分析:通过无标记3D质谱成像可视化细胞中的药物和代谢物吸收

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摘要

Detecting metabolites and parent compound within a cell type is now a priority for pharmaceutical development. In this context, three-dimensional secondary ion mass spectrometry (SIMS) imaging was used to investigate the cellular uptake of the antiarrhythmic agent amiodarone, a phospholipidosis-inducing pharmaceutical compound. The high lateral resolution and 3D imaging capabilities of SIMS combined with the multiplex capabilities of ToF mass spectrometric detection allows for the visualization of pharmaceutical compound and metabolites in single cells. The intact, unlabeled drug compound was successfully detected at therapeutic dosages in macrophages (cell line: NR8383). Chemical information from endogenous biomolecules was used to correlate drug distributions with morphological features. From this spatial analysis, amiodarone was detected throughout the cell with the majority of the compound found in the membrane and subsurface regions and absent in the nuclear regions. Similar results were obtained when the macrophages were doped with amiodarone metabolite, desethylamiodarone. The FWHM lateral resolution measured across an intracellular interface in a high lateral resolution ion images was approximately 550 nm. Overall, this approach provides the basis for studying cellular uptake of pharmaceutical compounds and their metabolites on the single cell level.
机译:现在,检测细胞类型内的代谢物和母体化合物是药物开发的重点。在这种情况下,三维二次离子质谱(SIMS)成像用于研究抗心律失常药胺碘酮(一种诱导磷脂的药物化合物)的细胞摄取。 SIMS的高横向分辨率和3D成像功能与ToF质谱检测的多重功能相结合,可以可视化单个细胞中的药物化合物和代谢物。在巨噬细胞中以治疗剂量成功检测到完整,未标记的药物化合物(细胞系:NR8383)。来自内源性生物分子的化学信息用于将药物分布与形态特征相关联。通过这种空间分析,在整个细胞中均检测到胺碘酮,其中大部分化合物存在于膜和地下区域,而在核区域则不存在。当巨噬细胞掺有胺碘酮代谢产物去乙基胺碘酮时,获得了相似的结果。在高横向分辨率离子图像中跨细胞内界面测量的FWHM横向分辨率约为550 nm。总的来说,该方法为研究细胞在单细胞水平上摄取药物及其代谢物提供了基础。

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