Cellular uptake and distribution of cobalt complexes of fluorescent ligands.
The development of complexes that allow the monitoring of the release and distribution of fluorescent models of anticancer drugs initially bound to cobalt(III) moieties is reported. Strong quenching of fluorescence upon ligation to cobalt(III) was observed for both the carboxylate- and the hydroximate-bound fluorophores as was the partial return of fluorescence following addition of ascorbate and cysteine. The extent of the increase in the fluorescence intensity observed following addition of these potential reductants is indicative of the fluorophore being displaced from the complex by the action of ascorbate or cysteine, by ligand exchange. The cellular distribution of the fluorescence revealed that coordination to cobalt can dramatically alter the subcellular distribution of a bound fluorophore. This work shows that fluorescence can be an effective means of monitoring these agents in cells, and of determining their sites of activation. The results also reveal that the cytotoxicity of such agents correlates with their uptake and distribution patterns and that these are influenced by the types of ligands attached to the complex.
Yamamoto
Natsuho
N
Centre for Heavy Metals Research, School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.
Danos
Sarah
S
Bonnitcha
Paul D
PD
Failes
Timothy W
TW
New
Elizabeth J
EJ
Hambley
Trevor W
TW
D001205:Ascorbic Acid / Q000737:chemistry; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003035:Cobalt / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D004563:Electrochemistry; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D008024:Ligands; D018613:Microscopy, Confocal; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D013997:Time Factors; D014018:Tissue Distribution
D005456:Fluorescent Dyes; D008024:Ligands; D009942:Organometallic Compounds; D003035:Cobalt; D003545:Cysteine; D001205:Ascorbic Acid