1. Photodynamic efficiency of diethylene glycol-linked glycoconjugated porphyrins in human retinoblastoma cells.
- Author
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Laville I, Pigaglio S, Blais JC, Doz F, Loock B, Maillard P, Grierson DS, and Blais J
- Subjects
- Animals, Carbohydrate Conformation, Carbohydrate Sequence, Cell Line, Tumor, Cell Survival drug effects, Cell Survival physiology, Drug Screening Assays, Antitumor, Galactosides chemical synthesis, Galactosides chemistry, Glycosylation, Humans, In Vitro Techniques, Mice, Molecular Sequence Data, Molecular Structure, Photosensitizing Agents chemistry, Porphyrins chemical synthesis, Porphyrins chemistry, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Structure-Activity Relationship, Ethylene Glycols chemistry, Galactosides pharmacology, Photochemotherapy methods, Photosensitizing Agents pharmacology, Porphyrins pharmacology, Retinoblastoma drug therapy
- Abstract
Photodynamic therapy (PDT) is emerging as a new strategy for the conservative treatment of hereditary retinoblastoma. The glycoconjugated porphyrins TPP(p-Deg-O-alpha-GalOH)(3), TPP(p-Deg-O-beta-GalOH)(3), TPP(p-Deg-O-alpha-ManOH)(3), and their S-analogues were synthesized to obtain efficient photosensitizers with some retinoblastoma cell affinity. In these systems, a sugar motif and porphyrin core were linked by a diethylene glycol spacer (Deg). Cellular uptake, localization, and photoactivity have been examined in human retinoblastoma cells (Y79). After preincubation with corresponding glycosylated albumin, the uptake of TPP(p-Deg-O-beta-GalOH)(3) and TPP(p-Deg-O-alpha-ManOH)(3) was 40-45% inhibited, indicating a possible cell-sugar-receptor saturation. High photoactivity was observed for the two alpha-galacto/manno porphyrins 8 and 10 (LD(50) = 0.05 and 0.35 muM, respectively) at 514 nm and low fluence (1 J/cm(2)). Analysis by MALDI-TOF mass spectrometry only indicated a small metabolic cleavage of the O-glycoconjugates and a good stability of the S-glycoside porphyrins. On the basis of these in vitro data, TPP(p-Deg-O-alpha-GalOH)(3) and TPP(p-Deg-O-alpha-ManOH)(3) were selected for in vivo studies.
- Published
- 2006
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