Correlation between site II-specific human serum albumin (HSA) binding affinity and murine in vivo photosensitizing efficacy of some Photofrin components.
Human serum albumin (HSA) is one of the key components in human blood that may influence drug distribution. As such, it is important to know the affinity of any drug for albumin. Previously, Photofrin, a mixture of monomeric, dimeric and oligomeric porphyrins, has been subjected to HSA binding studies. However, due to its complex nature, binding studies on Photofrin or other hematoporphyrin derivatives with HSA are inconclusive. In this report, the binding properties of some components (dimers and trimers) of Photofrin and the relationship between murine photosensitizing efficacy and those binding properties were investigated. The interaction of these porphyrins with HSA was investigated by direct ultrafiltration and fluorescent titration techniques with fluorescent probes such as dansyl-L-proline (DP), which is known to interact selectively with site II on HSA. Porphyrins also were tested for antitumor activity in a mouse model following intravenous administration and exposure to laser light. Together, the results suggest that the photosensitizers that were preferentially bound to site II of HSA were most effective at controlling murine tumor regrowth.
Tsuchida
T
T
Department of Radiation Biology, Roswell Park Cancer Institute, Buffalo, NY 14263-0001, USA.
Zheng
G
G
Pandey
R K
RK
Potter
W R
WR
Bellnier
D A
DA
Henderson
B W
BW
Kato
H
H
Dougherty
T J
TJ
D000818:Animals; D001665:Binding Sites; D017323:Dihematoporphyrin Ether / Q000378:metabolism*; D019281:Dimerization; D017324:Hematoporphyrin Derivative / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008811:Mice, Inbred DBA; D008956:Models, Chemical; D017319:Photosensitizing Agents / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D017319:Photosensitizing Agents; D012709:Serum Albumin; D017324:Hematoporphyrin Derivative; D017323:Dihematoporphyrin Ether