Gransbury, G.Kappen, P.Glover, C.Hughes, J.Levina, A.Lay, P.Musgrave, I.Harris, H.2016-11-132016-11-132016Metallomics, 2016; 8(8):762-7731756-59011756-591Xhttp://hdl.handle.net/2440/102464NAMI-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 mm). 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.enThis journal is © The Royal Society of Chemistry 2016Spheroids, CellularTumor Cells, CulturedHumansNeuroblastomaRutheniumRuthenium CompoundsOrganometallic CompoundsDimethyl SulfoxideIndazolesAntineoplastic AgentsX-Ray Absorption SpectroscopyTumor MicroenvironmentHypoxiaJournal article003005137610.1039/c6mt00145a0003814166000052-s2.0-84982090892260092Musgrave, I. [0000-0003-1016-0588]Harris, H. [0000-0002-3472-8628]