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Issue 5, 2016
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Multi-scale imaging of anticancer platinum(IV) compounds in murine tumor and kidney

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Abstract

Nano-scale secondary ion mass spectrometry (NanoSIMS) enables trace element and isotope analyses with high spatial resolution. This unique capability has recently been exploited in several studies analyzing the subcellular distribution of Au and Pt anticancer compounds. However, these studies were restricted to cell culture systems. To explore the applicability to the in vivo setting, we developed a combined imaging approach consisting of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), NanoSIMS and transmission electron microscopy (TEM) suitable for multi-scale detection of the platinum distribution in tissues. Applying this approach to kidney and tumor samples upon administration of selected platinum(IV) anticancer prodrugs revealed uneven platinum distributions on both the organ and subcellular scales. Spatial platinum accumulation patterns were quantitatively assessed by LA-ICP-MS in histologically heterogeneous organs (e.g., higher platinum accumulation in kidney cortex than in medulla) and used to select regions of interest for subcellular-scale imaging with NanoSIMS. These analyses revealed cytoplasmic sulfur-rich organelles accumulating platinum in both kidney and malignant cells. Those in the tumor were subsequently identified as organelles of lysosomal origin, demonstrating the potential of the combinatorial approach for investigating therapeutically relevant drug concentrations on a submicrometer scale.

Graphical abstract: Multi-scale imaging of anticancer platinum(iv) compounds in murine tumor and kidney

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Publication details

The article was received on 16 Nov 2015, accepted on 22 Dec 2015 and first published on 03 Feb 2016


Article type: Edge Article
DOI: 10.1039/C5SC04383B
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Citation: Chem. Sci., 2016,7, 3052-3061
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    Multi-scale imaging of anticancer platinum(IV) compounds in murine tumor and kidney

    A. A. Legin, S. Theiner, A. Schintlmeister, S. Reipert, P. Heffeter, M. A. Jakupec, J. Mayr, H. P. Varbanov, C. R. Kowol, M. Galanski, W. Berger, M. Wagner and B. K. Keppler, Chem. Sci., 2016, 7, 3052
    DOI: 10.1039/C5SC04383B

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