Volume 59, Issue 3
Research Article

Unambiguous Intracellular Localization and Quantification of a Potent Iridium Anticancer Compound by Correlative 3D Cryo X‐Ray Imaging

Dr. José Javier Conesa

Corresponding Author

E-mail address: jconesa@cells.es

E-mail address: jj.conesa@cnb.csic.es

MISTRAL beamline, ALBA Synchrotron Light Source, Cerdanyola del Vallès, 08290 Barcelona, Spain

Current address: Department of Structure of Macromolecules, Centro Nacional de Biotecnología/CSIC, 28049 Madrid, Spain

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Dr. Yang Yang

ID16A beamline, ESRF-The European Synchrotron, 38043 Grenoble, France

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Dr. José L. Carrascosa

Department of Structure of Macromolecules, Centro Nacional de Biotecnología/CSIC, 28049 Madrid, Spain

Unidad Asociada de Nanobiotecnología CNB-CSIC-IMDEA, 28049 Madrid, Spain

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Dr. Peter Cloetens

ID16A beamline, ESRF-The European Synchrotron, 38043 Grenoble, France

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Dr. Eva Pereiro

MISTRAL beamline, ALBA Synchrotron Light Source, Cerdanyola del Vallès, 08290 Barcelona, Spain

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Dr. Ana M. Pizarro

Corresponding Author

E-mail address: ana.pizarro@imdea.org

IMDEA Nanociencia, Faraday 9, 28049 Madrid, Spain

Unidad Asociada de Nanobiotecnología CNB-CSIC-IMDEA, 28049 Madrid, Spain

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First published: 07 November 2019

Abstract

The iridium half‐sandwich complex [Ir(η51‐C5Me4CH2py)(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 50 nm resolution, and cryo hard X‐ray fluorescence tomography (cryo‐XRF), which provides the elemental sensitivity with a 70 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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