NDLI: Comparison of KP1019 and NAMI-A in tumour-mimetic environments

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Metallomics Vol - 8 Issue - 7

Metallomics Vol - 8 Issue - 6

Metallomics Vol - 8 Issue - 5

Metallomics Vol - 8 Issue - 4

Metallomics Vol - 8 Issue - 3

Metallomics Vol - 8 Issue - 2

Comparison of KP1019 and NAMI-A in tumour-mimetic environments

Content Provider	Royal Society of Chemistry (RSC)
Author	Hughes, James N. Glover, Chris J. Levina, Aviva Musgrave, Ian F. Gransbury, Gemma K. Harris, Hugh H. Lay, Peter A. Kappen, Peter
Copyright Year	2016
Abstract	NAMI-A and KP1019 are RuIII-based anti-metastatic and cytotoxic anti-cancer drugs, respectively, and have been proposed to be activated by reduction to RuII. The potential reduction of NAMI-A and KP1019 in the hypoxic environment of a tumour model of neuroblastoma was examined. Normoxic, hypoxic and necrotic tumour tissues were modelled by multicellular spheroids of SH-SY5Y human neuroblastoma cells of various diameters (50–800 μm). The variation in spheroid environment was confirmed with pimonidazole staining. Laser-ablation inductively-coupled plasma mass spectrometry showed KP1019 and NAMI-A penetration into the spheroid hypoxic region. XANES showed that the speciation of NAMI-A biotransformation products did not change significantly as hypoxia levels increased. KP1019 metabolites showed a correlation between the degree of spheroid hypoxia and the Ru K-edge energy consistent with either partial reduction of RuIII to RuII in tumour microenvironments, increased S/Cl coordination or a reduced fraction of polynuclear Ru species. EXAFS spectroscopy was undertaken in an attempt to distinguish between these scenarios but was inconclusive.
Starting Page	762
Ending Page	773
Page Count	12
File Format	HTM / HTML PDF
ISSN	17565901
Volume Number	8
Issue Number	8
Journal	Metallomics
DOI	10.1039/c6mt00145a
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	SH-SY5Y Spectroscopy Extended X-ray absorption fine structure X-ray absorption near edge structure Cytotoxicity Tumor hypoxia Spheroid Neuroblastoma Irreducible fraction Necrosis Blood plasma Metal K-edge Biotransformation Micrometre Mass spectrometry Speciation
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

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