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The accumulation, uptake mechanism, cytotoxicity, cellular localisation of—and mode of cell death induced by—dinuclear ruthenium(II) complexes DD/LL-[{Ru(phen)2}2{m-bbn}]4+ (Rubbn), where phen is 1,10-phenanthroline, bbn is bis[4(4’-methyl-2,2’- bipyridyl)]-1,n-alkane (n=2, 5, 7, 10, 12 or 16), and the corresponding mononuclear complexes containing the bbn ligands, were studied in L1210 murine leukaemia cells. Cytotoxicity increased with linker chain length, and the DD-Rubb16 complex displayed the highest cytotoxicity of the series, with an IC50 value of 5 mm, similar to that of carboplatin in the L1210 murine leukaemia cell line. Confocal microscopy and flow cytometry studies indicated that the complexes accumulate in the mitochondria of L1210 cells, with the magnitude of cellular uptake and accumulation increasing with linking chain length in the bbn bridge of the metal complex. DD-Rubb16 entered the L1210 cells by passive diffusion (with a minor contribution from protein-mediated active transport), inducing cell death via apoptosis. Additionally, metal-complex uptake in leukaemia cells was approximately 16-times that observed in healthy B cells highlighting that the bbn series of complexes may have potential as selective anticancer drugs.

Item Type:	Refereed Article
Keywords:	apoptosis, bioinorganic chemistry, cellular uptake, cytotoxicity, ruthenium polypyridyl complexes
Research Division:	Biomedical and Clinical Sciences
Research Group:	Immunology
Research Field:	Immunology not elsewhere classified
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Korner, H (Professor Heinrich Korner)
ID Code:	72466
Year Published:	2011
Web of Science® Times Cited:	62
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2011-08-26
Last Modified:	2012-03-26
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