title: Redistribution of Foscan from plasma proteins to model membranes.
abstract: Photodynamic therapy is a comparatively novel modality of tumours treatment that includes simultaneous action of photosensitizers, light and oxygen. Photosensitizer redistribution between plasma proteins and biomembranes define photosensitizers interaction with cells, their intracellular localization and kinetics of sensitizers accumulation in the tumour. Present study investigates the kinetics of Foscan release from plasma proteins to model membranes using fluorescence resonance energy transfer (FRET) from label, covalently bound to protein, to sensitizer. We have demonstrated very slow kinetics of Foscan release from protein complexes with rate constants of (1.7 +/- 0.1) x 10(-3) s(-1) for albumin and (1.6 +/- 0.3) x 10(-4) s(-1) for high-density lipoproteins (HDL). Foscan redistributes by both collision and diffusion-mediated transfer from complexes with HDL, with bimolecular rate constant k(out) = (8.8 +/- 1.4) x 10(-2) M(-1) s(-1). Thermodynamic considerations proposed that sensitizer release from HDL into the aqueous medium is unfavourable and collision mechanism appeared to be a preferred mode of transfer in biological environment. Slow rates of Foscan redistribution from plasma proteins should be considered while planning dosimetry protocol of Foscan-PDT.
authors.affiliation: Centre Alexis Vautrin, CRAN UMR 7039 CNRS-INPL-UHP, Avenue de Bourgogne, 54511, Vandoeuvre-Les-Nancy cedex, France.
authors.forename: Siarhei
authors.initials: S
authors.lastname: Sasnouski
authors.forename: Dzmitry
authors.initials: D
authors.lastname: Kachatkou
authors.forename: Vladimir
authors.initials: V
authors.lastname: Zorin
authors.forename: François
authors.initials: F
authors.lastname: Guillemin
authors.forename: Lina
authors.initials: L
authors.lastname: Bezdetnaya
mesh_terms: D001665:Binding Sites; D001798:Blood Proteins / Q000737:chemistry*; D008076:Cholesterol, HDL / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D007700:Kinetics; D008055:Lipids / Q000737:chemistry; D008567:Membranes, Artificial; D008652:Mesoporphyrins / Q000737:chemistry*; D008958:Models, Molecular; D017319:Photosensitizing Agents / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013816:Thermodynamics
chemical_list: D001798:Blood Proteins; D008076:Cholesterol, HDL; D008055:Lipids; D008567:Membranes, Artificial; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin