The 2-aminoglucosamide motif improves cellular uptake and photodynamic activity of tetraphenylporphyrin.
Several strategies have been proposed to improve the efficiency of photosensitizers used in photodynamic therapy (PDT). In this context, the synthesis of mono- (1) and di-glucosylated (2) porphyrins, and mono-glucosylated chlorin (3) was performed. HT29 human adenocarcinoma cells were significantly more sensitive to asymmetric and less hydrophobic glucosylated photosensitizers-mediated PDT (1, 3), compared to tetraphenylporphyrin (TPP). The lowest photosensitivity observed for TPP was consistent with the lowest uptake. Moreover, the most pronounced photodynamic activity measured for 3 was in relation with the improvement of cellular uptake, the singlet oxygen quantum yield and the high extinction coefficient value at 650 nm compared to porphyrins. Cellular localization analysis showed that 1 and 3 accumulated mainly inside the endoplasmic reticulum.
Di Stasio
Benoît
B
DCPR-GRAPP, UMR 7630 CNRS-INPL, Groupe ENSIC, 1, rue Grandville, 54000 Nancy, France.
Frochot
Céline
C
Dumas
Dominique
D
Even
Pascale
P
Zwier
Jurriaan
J
Müller
Audrey
A
Didelon
Jacques
J
Guillemin
François
F
Viriot
Marie-Laure
ML
Barberi-Heyob
Muriel
M
D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019073:HT29 Cells; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D009005:Monosaccharides / Q000138:chemical synthesis; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D013997:Time Factors
C507734:5,15-bis(4-(1,3,4,6-tetra-O-acetyl-2-amido-2-desoxy-beta-D-glucopyranose phenyl))-10,20-biphenyl porphyrin; C507733:5-(4-(1,3,4,6-tetra-O-acetyl-2-amido-2-desoxy-beta-D-glucopyranose phenyl))-10,15,20-triphenyl chlorin; C507731:5-(4-(1,3,4,6-tetra-O-acetyl-2-amido-2-desoxy-beta-D-glucopyranose phenyl))-10,15,20-triphenyl porphyrin; D009005:Monosaccharides; D017319:Photosensitizing Agents; D011166:Porphyrins; C409084:tetraphenylporphyrin; C006969:chlorin