Unambiguous Intracellular Localization and Quantification of a Potent Iridium Anticancer Compound by Correlative 3D Cryo X-Ray Imaging.
Angew Chem Int Ed Engl
; 59(3): 1270-1278, 2020 01 13.
Article
em En
| MEDLINE
| ID: mdl-31697000
ABSTRACT
The iridium half-sandwich complex [Ir(η5κ1 -C5 Me4 CH2 py)(2-phenylpyridine)]PF6 is highly cytotoxic 15-250× more potent than clinically used cisplatin in several cancer cell lines. We have developed a correlative 3D cryo X-ray imaging approach to specifically localize and quantify iridium within the whole hydrated cell at nanometer resolution. By means of cryo soft X-ray tomography (cryo-SXT), which provides the cellular ultrastructure at 50â
nm resolution, and cryo hard X-ray fluorescence tomography (cryo-XRF), which provides the elemental sensitivity with a 70â
nm step size, we have located the iridium anticancer agent exclusively in the mitochondria. Our methodology provides unique information on the intracellular fate of the metallodrug, without chemical fixation, labeling, or mechanical manipulation of the cells. This cryo-3D correlative imaging method can be applied to a number of biochemical processes for specific elemental localization within the native cellular landscape.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Tomografia por Raios X
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Irídio
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Neoplasias
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article