Cellular delivery and retention of Photofrin II: the effects of interaction with human plasma proteins.
The absorbance and fluorescence spectra of Photofrin II (PII) in the presence of albumin, globulins and lipoproteins from human plasma show that all of these proteins induce a degree of disaggregation of PII material. In addition, there are substantial rearrangements in the distribution of different fractions contained in PII and their binding to the protein. It is shown that these rearrangements have considerable impact on the uptake of PII by cultured cells and the ensuing retention of the drug in the cells. The information on the contribution of fluorescing and non-fluorescing components of PII in the cells was obtained by measuring first the PII fluorescence in suspensions of live cells, followed by chemical extraction of porphyrin material from the same cells. The interaction of PII with low density lipoproteins resulted in markedly lower levels of PII material retained in the cells, compared to protein-free drug exposure. Somewhat better but still inferior PII retention was observed with high density lipoproteins. The samples with very low density lipoproteins showed increased uptake of PII, but the subsequent retention of the drug was low, so that the remaining amount of the drug was not much different than in protein-free samples. The strongest inhibition of PII uptake was seen with albumin, with ensuing retention of PII not significantly different than in protein-free samples. The best retention of PII was observed with globulins, with approx. 25% higher total drug content retained in the cells after long-term clearance relative to protein-free samples.
Korbelik
M
M
Cancer Imaging, British Columbia Cancer Research Centre, Vancouver, Canada.
Hung
J
J
D001693:Biological Transport, Active; D001798:Blood Proteins / Q000378:metabolism*; D017323:Dihematoporphyrin Ether; D006367:HeLa Cells; D006415:Hematoporphyrins / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D010777:Photochemistry; D011485:Protein Binding; D013050:Spectrometry, Fluorescence
D001798:Blood Proteins; D006415:Hematoporphyrins; D017323:Dihematoporphyrin Ether