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

Chemical Science
Anton LeginBernhard K Keppler

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 tu...Continue Reading

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Citations

Jan 4, 2020·Proceedings of the National Academy of Sciences of the United States of America·Ka-Chung TongChi-Ming Che
Feb 6, 2017·Metallomics : Integrated Biometal Science·Ronald F S LeePaul J Dyson
Jul 25, 2020·Current Protocols in Cell Biology·Derek P Narendra, Matthew L Steinhauser
Sep 16, 2017·Metallomics : Integrated Biometal Science·Ronald F S LeePaul J Dyson
Feb 4, 2021·Current Opinion in Chemical Biology·Sarah TheinerGunda Koellensperger
May 22, 2021·Chemical Reviews·Philip A DobleDavid Clases
Nov 6, 2018·Biomacromolecules·Claudia BattistellaHarm-Anton Klok
Nov 19, 2021·The Journal of Physical Chemistry. a·Rongji ZhuJiawei Xu

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Methods Mentioned

BETA
transmission electron microscopy
electron microscopy
fluorescence microscopy
imaging technique
biopsies
Transmission

Software Mentioned

GraphPad
GNU
NanoSIMS
GIMP
GraphPad Prism
Igor Pro
Agilent MassHunter
WinImage
iTEM

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