Metallomics for drug development: an integrated CE-ICP-MS and ICP-MS approach reveals the speciation changes for an investigational ruthenium(III) drug bound to holo-transferrin in simulated cancer cytosol

Svetlana S. Aleksenko , Magdalena Matczuk , Xifeng Lu , Lidia S. Foteeva , Katarzyna Pawlak , Andrei R. Timerbaev , Maciej Jarosz

Abstract

A method based on combining inductively coupled plasma mass spectrometry (ICP-MS) with capillary electrophoresis (CE) or an ultrafiltration step was developed to study the speciation of the serum-protein adducts of a ruthenium anticancer drug under in vitro intracellular conditions. The formation of a reactive Ru species in the cell, following the metal release from the protein, is thought to play an important role in the drug's mode of action. Glutathione and ascorbic acid at their cancer cytosol concentrations were shown to be capable of altering the metal speciation in the drug adduct with holo-transferrin but not that with albumin. The appearance of the additional peaks in ICP-MS electropherograms (by recording both Ru- and Fe-specific signals) was found to be dependent on time which allowed for kinetic assessment of the evolution of novel metal species. On the contrary, after the addition of citric acid the ruthenium ion (within the appropriately complexed scaffold) remained sequestered in the adduct. This was inferred as a proof of the speciation changes taking place by a virtue of a redox mechanism rather than due to ligand-exchange transformations. The protein-bound metallodrug was further characterized by direct ICP-MS assaying so as to confirm a partial release of ruthenium induced by glutathione.
Author Svetlana S. Aleksenko - [Vernadsky Institute of Geochemistry and Analytical Chemistry of Russian Academу of Sciences]
Svetlana S. Aleksenko,,
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, Magdalena Matczuk (FC / CAC)
Magdalena Matczuk,,
- Chair Of Analytical Chemistry
, Xifeng Lu (FC / CAC)
Xifeng Lu,,
- Chair Of Analytical Chemistry
, Lidia S. Foteeva - [Vernadsky Institute of Geochemistry and Analytical Chemistry of Russian Academу of Sciences]
Lidia S. Foteeva,,
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, Katarzyna Pawlak (FC / CAC)
Katarzyna Pawlak,,
- Chair Of Analytical Chemistry
, Andrei R. Timerbaev - [Vernadsky Institute of Geochemistry and Analytical Chemistry of Russian Academу of Sciences]
Andrei R. Timerbaev,,
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, Maciej Jarosz (FC / CAC)
Maciej Jarosz,,
- Chair Of Analytical Chemistry
Journal seriesMetallomics, ISSN 1756-5901
Issue year2013
Vol5
No8
Pages955-963
Publication size in sheets0.5
ASJC Classification2506 Metals and Alloys; 1303 Biochemistry; 2502 Biomaterials; 1304 Biophysics; 1601 Chemistry (miscellaneous)
DOIDOI:10.1039/C3MT00092C
URL http://pubs.rsc.org/en/content/articlelanding/2013/mt/c3mt00092c#!divAbstract
Languageen angielski
File
wdpb_publikacje_pliki_plik_publikacja_1835_org.pdf 1.73 MB
Score (nominal)35
Score sourcejournalList
ScoreMinisterial score = 35.0, 01-02-2020, ArticleFromJournal
Ministerial score (2013-2016) = 35.0, 01-02-2020, ArticleFromJournal
Publication indicators WoS Citations = 24; Scopus Citations = 24; Scopus SNIP (Source Normalised Impact per Paper): 2014 = 1.09; WoS Impact Factor: 2013 = 3.978 (2) - 2013=4.01 (5)
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