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Unambiguous Intracellular Localization and Quantification of a Potent Iridium Anticancer Compound by Correlative 3D Cryo X‐Ray Imaging
Author(s) -
Conesa José Javier,
Carrasco Ana C.,
RodríguezFanjul Vanessa,
Yang Yang,
Carrascosa José L.,
Cloetens Peter,
Pereiro Eva,
Pizarro Ana M.
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201911510
Subject(s) - iridium , correlative , fluorescence lifetime imaging microscopy , chemistry , intracellular , fluorescence , biophysics , cancer cell lines , fluorescence microscope , resolution (logic) , x ray , cancer cell , nanotechnology , materials science , biochemistry , biology , cancer , computer science , physics , philosophy , linguistics , quantum mechanics , artificial intelligence , catalysis , genetics
The iridium half‐sandwich complex [Ir(η 5 :κ 1 ‐C 5 Me 4 CH 2 py)(2‐phenylpyridine)]PF 6 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.