pH, serum proteins and ionic strength influence the uptake of merocyanine 540 by WiDr cells and its interaction with membrane structures.
It has been suggested that selective uptake of photosensitizers is due to significantly lower pH of the interstitial fluid in tumors compared to normal tissue. Therefore, the cellular uptake of merocyanine 540 (MC 540) was examined at two pH values: 6.8+/-0.1 and 7.4+/-0.1. There was no difference in spectral properties (absorption and fluorescence maxima positions, fluorescence intensity) of the drug in the presence of increasing amounts of either human blood plasma or FCS (0-2%) at the two pH values investigated. Nevertheless, significantly higher amounts of the drug were taken up by WiDr cells at pH 6.8+/-0.1, both in the presence of 10% FCS and in the absence of FCS. The absorption spectra of MC 540 in the presence of egg phosphatidylcholine (PC) liposomes turned out to be NaCl concentration-dependent (0.00-0.30 mol l(-1)). Membrane fluidity, as measured by fluorescence anisotropy of diphenylhexatriene (DPH), was unchanged within the experimental error in the NaCl concentration range 0.01-0.30 mol l(-1). The spectral changes indicated an enhancement of the incorporation of MC 540 into lipid membranes with increasing ionic strength. Such a salt concentration dependence suggests a possible involvement of the surface potential in the interaction of MC 540 with lipid membranes. The results might provide an explanation of the pH dependency of the cellular uptake of MC 540 observed in this study.
Cunderlíková
Beata
B
Department of Biophysics, Institute for Cancer Research, Montebello, N-0310 Oslo, Norway. beatacu@labmed.uio.no
Sikurová
Libusa
L
Moan
Johan
J
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D001798:Blood Proteins / Q000378:metabolism*; D021961:Cell Membrane Structures / Q000737:chemistry / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D003470:Culture Media / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007477:Ions; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D011744:Pyrimidinones / Q000737:chemistry / Q000493:pharmacokinetics*; D013050:Spectrometry, Fluorescence; D014407:Tumor Cells, Cultured
D001798:Blood Proteins; D003470:Culture Media; D007477:Ions; D008051:Lipid Bilayers; D008081:Liposomes; D017319:Photosensitizing Agents; D011744:Pyrimidinones; C003954:merocyanine dye