Method to Investigate the Distribution of Water-Soluble Drug-Delivery Systems in Fresh Frozen Tissues Using Imaging Mass Cytometry.

Autor:	Strittmatter N; Imaging and Data Analytics, Clinical Pharmacology and Safety Sciences, R&D BioPharmaceuticals, AstraZeneca, Cambridge CB2 0AA, U.K., England RM; Advanced Drug Delivery, Pharmaceutical Sciences, R&D BioPharmaceuticals, AstraZeneca, Macclesfield SK10 2NA, U.K., Race AM; Institute of Medical Bioinformatics and Biostatistics, Philipps University of Marburg, Marburg 35037, Germany., Sutton D; Imaging and Data Analytics, Clinical Pharmacology and Safety Sciences, R&D BioPharmaceuticals, AstraZeneca, Cambridge CB2 0AA, U.K., Moss JI; Bioscience, Discovery, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, U.K., Maglennon G; Oncology Safety, Clinical Pharmacology and Safety Sciences, R&D BioPharmaceuticals, AstraZeneca, Cambridge CB2 0AA, U.K., Ling S; Imaging and Data Analytics, Clinical Pharmacology and Safety Sciences, R&D BioPharmaceuticals, AstraZeneca, Cambridge CB2 0AA, U.K., Wong E; Antibody Discovery and Protein Engineering, R&D, AstraZeneca, Cambridge CB2 0AA, U.K., Rose J; Animal Sciences and Technologies, Clinical Pharmacology and Safety Sciences, R&D BioPharmaceuticals, AstraZeneca, Cambridge CB2 0AA, U.K., Purvis I; Animal Sciences and Technologies, Clinical Pharmacology and Safety Sciences, R&D BioPharmaceuticals, AstraZeneca, Cambridge CB2 0AA, U.K., Macdonald R; Animal Sciences and Technologies, Clinical Pharmacology and Safety Sciences, R&D BioPharmaceuticals, AstraZeneca, Cambridge CB2 0AA, U.K., Barry ST; Bioscience, Discovery, Oncology R&D, AstraZeneca, Cambridge CB2 0AA, U.K., Ashford MB; Advanced Drug Delivery, Pharmaceutical Sciences, R&D BioPharmaceuticals, AstraZeneca, Macclesfield SK10 2NA, U.K., Goodwin RJA; Imaging and Data Analytics, Clinical Pharmacology and Safety Sciences, R&D BioPharmaceuticals, AstraZeneca, Cambridge CB2 0AA, U.K.; Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, U.K.
Jazyk:	angličtina
Zdroj:	Analytical chemistry [Anal Chem] 2021 Mar 02; Vol. 93 (8), pp. 3742-3749. Date of Electronic Publication: 2021 Feb 19.
DOI:	10.1021/acs.analchem.0c03908
Abstrakt:	Imaging mass cytometry (IMC) offers the opportunity to image metal- and heavy halogen-containing xenobiotics in a highly multiplexed experiment with other immunochemistry-based reagents to distinguish uptake into different tissue structures or cell types. However, in practice, many xenobiotics are not amenable to this analysis, as any compound which is not bound to the tissue matrix will delocalize during aqueous sample-processing steps required for IMC analysis. Here, we present a strategy to perform IMC experiments on a water-soluble polysarcosine-modified dendrimer drug-delivery system (S-Dends). This strategy involves two consecutive imaging acquisitions on the same tissue section using the same instrumental platform, an initial laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MSI) experiment followed by tissue staining and a standard IMC experiment. We demonstrated that settings can be found for the initial ablation step that leave sufficient residual tissue for subsequent antibody staining and visualization. This workflow results in lateral resolution for the S-Dends of 2 μm followed by imaging of metal-tagged antibodies at 1 μm.
Databáze:	MEDLINE
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