Intracellular distribution and intracellular dynamics of a spin-labeled analogue of doxorubicin fluorescence and EPR spectroscopy.
Fluorescence spectroscopy revealed a dramatic difference between the intracellular distributions of doxorubicin (DOX) and its paramagnetic analogue, ruboxyl (Rb). Modification of the anthracyclin structure by introduction of a paramagnetic label at position 14 in the DOX molecule resulted in reduced DNA binding and enhanced partitioning into phospholipid membranes, as evidenced by the fluorescence-quenching experiments. Higher partitioning into cell membranes resulted in stronger intracellular fluorescence of Rb. In addition, a paramagnetic label on the Rb molecule provided a unique opportunity for an EPR investigation of the drug's intracellular distribution and dynamics. The observed changes in the EPR spectra of drug-containing cells during their life cycle suggested either a progressive release of the intercalated drug, cell membrane fluidization, or both.
Rapoport
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The Department of Bioengineering, University of Utah, Salt Lake City 84112, USA. natasha.rapoport@m.cc.utah.edu
Pitina
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D004247:DNA / Q000378:metabolism; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000378:metabolism; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D018922:HL-60 Cells; D006801:Humans; D008081:Liposomes; D013050:Spectrometry, Fluorescence; D013113:Spin Labels
D008081:Liposomes; D013113:Spin Labels; D004317:Doxorubicin; C042480:ruboxyl; D004247:DNA; D003630:Daunorubicin