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Issue 7, 2015
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Nuclear accumulation of anthracyclines in the endothelium studied by bimodal imaging: fluorescence and Raman microscopy

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Abstract

Anthracycline antibiotics display genotoxic activity towards cancer cells but their clinical utility is limited by their cardiac and vascular toxicity. The aim of this study was to develop a Raman-based methodology to study the nuclear accumulation of anthracyclines in the endothelium. For this purpose bimodal confocal Raman and fluorescence imaging was used to monitor cellular composition changes as a result of anthracycline exposure on endothelial cells (EA.hy926), and nuclear drug accumulation, respectively. Simultaneously effects of anthracyclines on endothelium viability were investigated by caspases-3 and -7 and MTT assays. We demonstrated that nuclear accumulation of DOX and EDOX was similar; however, EDNR accumulated in endothelial nuclei at concentrations 10 times higher than DNR. In turn, epimers of DOX or DNR were both consistently less toxic on the endothelium as compared to their congeners as evidenced by MTT and caspase assays. In summary, bimodal Raman and fluorescence-based nucleus profiling proves to be a valuable tool to study structure-activity relationship of nuclear accumulation and toxicity of anthracyclines in endothelium.

Graphical abstract: Nuclear accumulation of anthracyclines in the endothelium studied by bimodal imaging: fluorescence and Raman microscopy

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Publication details

The article was received on 17 Oct 2014, accepted on 17 Dec 2014 and first published on 05 Jan 2015


Article type: Paper
DOI: 10.1039/C4AN01882F
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Citation: Analyst, 2015,140, 2302-2310

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    Nuclear accumulation of anthracyclines in the endothelium studied by bimodal imaging: fluorescence and Raman microscopy

    K. Majzner, T. Wojcik, E. Szafraniec, M. Lukawska, I. Oszczapowicz, S. Chlopicki and M. Baranska, Analyst, 2015, 140, 2302
    DOI: 10.1039/C4AN01882F

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