Distribution of chlorophyll- and bacteriochlorophyll-derived photosensitizers in human blood plasma.
Chlorophyll a and, in particular, bacteriochlorophyll a derivatives are promising candidates for photosensitizers in photodynamic therapy. The distribution of 21 (bacterio)chlorophyll derivatives among human blood plasma fractions was studied by iodixanol gradient ultracentrifugation and in situ absorption spectroscopy. Modifications of the natural pigments involved the central metal (Mg(2+), Zn(2+), Pd(2+), none), the isocyclic ring (closed, open and taurinated), substituents at C-3 (vinyl, acetyl, 1-hydroxyethyl) and C-17(3) (phytyl ester, free acid). Cellular blood components bound only a small fraction of the pigments. Distribution among low-density lipoproteins (LDL), high-density lipoproteins (HDL) and high-density proteins (HDP) of the plasma was influenced as follows: (1) application in Cremophor((R)) EL slightly altered pigment distribution by lipoprotein modification, (2) only very polar pigments with multiple hydrophilic substituents showed substantial HDP binding, (3) the presence of the esterifying alcohol at C-17(3) caused enrichment in LDL, this was more pronounced with bacteriochlorophylls than with chlorophylls, (4) substituents at C-3 had only little influence on the distribution, (5) Zn(2+)-complexes were enriched in HDL compared to Mg(2+) and Pd(2+) complexes, indicating specific binding of the former. Equilibration of pigments among the different fractions was largely complete within 3 h.
Dandler
Jörg
J
Department Biologie I-Botanik, Universität München, Munich, Germany.
Wilhelm
Brigitte
B
Scheer
Hugo
H
D001429:Bacteriochlorophylls / Q000737:chemistry*; D002734:Chlorophyll / Q000737:chemistry*; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D015394:Molecular Structure; D017319:Photosensitizing Agents / Q000097:blood*; D010949:Plasma / Q000737:chemistry*; D011485:Protein Binding; D013057:Spectrum Analysis; D014461:Ultracentrifugation
D001429:Bacteriochlorophylls; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D017319:Photosensitizing Agents; D002734:Chlorophyll