title: Dynamics of interactions of photosensitizers with lipoproteins and membrane-models: correlation with cellular incorporation and subcellular distribution.
abstract: The incorporation and subcellular localization of photosensitizers are critical determinants of their efficiency. Here, we correlate these properties with the interactions of photosensitizers with membrane-models and low density lipoproteins (LDL) in acellular systems. Focus was given on dynamics aspects. Two amphiphilic photosensitizers, deuteroporphyrin (DP) and aluminum phthalocyanine sulfonated on two adjacent isoindole units (AlPcS2a) were selected. The phthalocyanine was bound to LDL with an overall association constant around 5 x 10(7)M(-1). Biphasic association kinetics was indicative of two types of sites. The release of the phthalocyanine into the bulk aqueous medium occurred within less than a second. A similar behavior was found previously for deuteroporphyrin although its affinity was somewhat higher (5.5 x 10(8)M(-1)). Both compounds were previously characterized by high affinity for membrane-models and quick exchange with the bulk solution. However, they strongly differed by their rate of transfer through the lipid bilayer, in the range of seconds for the porphyrin, several hours for the phthalocyanine. In the case of the porphyrin, fluorescence microscopy on human fibroblasts showed diffuse labeling with no significant modification of the distribution upon vectorization by LDL. In contrast, the phthalocyanine was localized in intracellular vesicles. Vectorization by LDL favored lysosomal localization although little effect was found on the overall uptake as shown by extraction experiments. The role of lipoproteins in the cellular localization of photosensitizers is significantly more important for photosensitizers not freely diffusing through bilayers. The dynamics of the interactions of photosensitizers with membranes appears as an important determinant of their subcellular localization.
authors.affiliation: Laboratoire de Physicochimie Biomoléculaire et Cellulaire, Université Pierre et Marie Curie, CNRS UMR 7033, 75005 Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bonneau
authors.forename: Patrice
authors.initials: P
authors.lastname: Morlière
authors.forename: Daniel
authors.initials: D
authors.lastname: Brault
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003905:Deuteroporphyrins / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000378:metabolism; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009942:Organometallic Compounds / Q000378:metabolism; D017319:Photosensitizing Agents / Q000378:metabolism*; D013347:Subcellular Fractions
chemical_list: D003905:Deuteroporphyrins; D007211:Indoles; D008077:Lipoproteins, LDL; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C028839:deuteroporphyrin-IX; C064331:aluminum phthalocyanine disulfonate