Mechanism of cellular uptake of a ruthenium polypyridyl complex.
Transition metal complexes provide a promising avenue for the design of therapeutic and diagnostic agents, but the limited understanding of their cellular uptake is a roadblock to their effective application. Here, we examine the mechanism of cellular entry of a luminescent ruthenium(II) polypyridyl complex, Ru(DIP) 2dppz (2+) (where DIP = 4,7-diphenyl-1,10-phenanthroline and dppz = dipyridophenazine), into HeLa cells, with the extent of uptake measured by flow cytometry. No diminution of cellular uptake is observed under metabolic inhibition with deoxyglucose and oligomycin, indicating an energy-independent mode of entry. The presence of organic cation transporter inhibitors also does not significantly alter uptake. However, the cellular internalization of Ru(DIP) 2dppz (2+) is sensitive to the membrane potential. Uptake decreases when cells are depolarized with high potassium buffer and increases when cells are hyperpolarized with valinomycin. These results support passive diffusion of Ru(DIP) 2dppz (2+) into the cell.
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Cindy A
CA
Puckett
Jacqueline K
JK
Barton
D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D005434:Flow Cytometry / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008954:Models, Biological; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D017680:Potassium Compounds / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry*; D014634:Valinomycin / Q000494:pharmacology
D009942:Organometallic Compounds; D017680:Potassium Compounds; D014634:Valinomycin; D012428:Ruthenium