Photodynamic efficiency of diethylene glycol-linked glycoconjugated porphyrins in human retinoblastoma cells.
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.
Laville
Isabelle
I
BIOMOCETI, UMR CNRS 7033/Université Pierre et Marie Curie, 4 place Jussieu, F-75252 Paris Cedex 05, France.
Pigaglio
Sophie
S
Blais
Jean-Claude
JC
Doz
François
F
Loock
Bernard
B
Maillard
Philippe
P
Grierson
David S
DS
Blais
Jocelyne
J
D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004354:Drug Screening Assays, Antitumor; D005026:Ethylene Glycols / Q000737:chemistry*; D005697:Galactosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006031:Glycosylation; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012175:Retinoblastoma / Q000188:drug therapy*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship
C510301:5,10,15-tri(4-O-(2-(2-(2-O-galactosyloxy)ethoxy)ethoxy)phenyl)-20-phenylporphyrin; C510302:5,10,15-tri(4-O-(2-(2-(2-mannosyloxy)ethoxy)ethoxy)phenyl)-20-phenylporphyrin; D005026:Ethylene Glycols; D005697:Galactosides; D017319:Photosensitizing Agents; D011166:Porphyrins; C013484:diethylene glycol