Subcellular Mass Spectrometry Imaging and Absolute Quantitative Analysis across Organelles.

Autor:	Thomen A; Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, 412 96, Sweden., Najafinobar N; Medicinal Chemistry, Research and Early Development, Respiratory, Inflammation, and Autoimmune, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 430 51, Sweden., Penen F; Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Gothenburg, 412 96, Sweden., Kay E; Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 430 51, Sweden., Upadhyay PP; Pharmaceutical Technolgy and Development, AstraZeneca R&D, Gothenburg, 430 52, Sweden., Li X; Center for Imaging and Systems Biology, College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China., Phan NTN; Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, 412 96, Sweden., Malmberg P; Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Gothenburg, 412 96, Sweden., Klarqvist M; Early Product Development, Pharmaceutical Science, R&D, AstraZeneca, Gothenburg, 431 50, Sweden., Andersson S; New Modalities, Discovery Sciences, R&D, AstraZeneca, Gothenburg, 430 51, Sweden., Kurczy ME; DMPK, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 430 51, Sweden., Ewing AG; Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, 412 96, Sweden.
Jazyk:	angličtina
Zdroj:	ACS nano [ACS Nano] 2020 Apr 28; Vol. 14 (4), pp. 4316-4325. Date of Electronic Publication: 2020 Apr 08.
DOI:	10.1021/acsnano.9b09804
Abstrakt:	Mass spectrometry imaging is a field that promises to become a mainstream bioanalysis technology by allowing the combination of single-cell imaging and subcellular quantitative analysis. The frontier of single-cell imaging has advanced to the point where it is now possible to compare the chemical contents of individual organelles in terms of raw or normalized ion signal. However, to realize the full potential of this technology, it is necessary to move beyond this concept of relative quantification. Here we present a nanoSIMS imaging method that directly measures the absolute concentration of an organelle-associated, isotopically labeled, pro-drug directly from a mass spectrometry image. This is validated with a recently developed nanoelectrochemistry method for single organelles. We establish a limit of detection based on the number of isotopic labels used and the volume of the organelle of interest, also offering this calculation as a web application. This approach allows subcellular quantification of drugs and metabolites, an overarching and previously unmet goal in cell science and pharmaceutical development.
Databáze:	MEDLINE
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