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Synchrotron X‐Ray Fluorescence Nanoprobe Reveals Target Sites for Organo‐Osmium Complex in Human Ovarian Cancer Cells
Author(s) -
SanchezCano Carlos,
RomeroCanelón Isolda,
Yang Yang,
HandsPortman Ian J.,
Bohic Sylvain,
Cloetens Peter,
Sadler Peter J.
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201605911
Subject(s) - nanoprobe , mitochondrion , chemistry , fluorescence , endoplasmic reticulum , cancer cell , cell , cytoplasm , cancer research , biophysics , cancer , biochemistry , biology , genetics , physics , quantum mechanics
A variety of transition metal complexes exhibit anticancer activity, but their target sites in cells need to be identified and mechanisms of action elucidated. Here, it was found that the sub‐cellular distribution of [Os(η 6 ‐ p ‐cym)(Azpy‐NMe 2 )I] + ( p ‐cym= p ‐cymene, Azpy‐NMe 2 =2‐( p ‐[dimethylamino]phenylazo)pyridine) ( 1 ), a promising drug candidate, can be mapped in human ovarian cancer cells at pharmacological concentrations using a synchrotron X‐ray fluorescence nanoprobe (SXRFN). SXRFN data for Os, Zn, Ca, and P, as well as TEM and ICP analysis of mitochondrial fractions suggest localization of Os in mitochondria and not in the nucleus, accompanied by mobilization of Ca from the endoplasmic reticulum, a signaling event for cell death. These data are consistent with the ability of 1 to induce rapid bursts of reactive oxygen species and especially superoxide formed in the first step of O 2 reduction in mitochondria. Such metabolic targeting differs from the action of Pt drugs, offering promise for combatting Pt resistance, which is a current clinical problem.