Interest of RGD-containing linear or cyclic peptide targeted tetraphenylchlorin as novel photosensitizers for selective photodynamic activity

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• 作者：Cé ; line Frochot ; Benoî ; t Di Stasio ; Ré ; gis V ; eresse ; Marie-José ; e Belgy ; Marc Dodeller ; Franç ; ois Guillemin ; Marie-Laure Viriot ; Muriel Barberi-Heyob
• 关键词：Chlorin ; Porphyrin ; RGD ; Solid-phase synthesis ; Singlet oxygen quantum yield ; HUVEC ; EMT-6 ; α ; _vβ ; ₃ integrin
• 刊名：Bioorganic Chemistry
• 出版年：2007
• 出版时间：June 2007
• 年：2007
• 卷：35
• 期：3
• 页码：205-220
• 全文大小：452 K

文摘

Destruction of the neovasculature is essential for tumor eradication by photodynamic therapy. Since the over-expression of integrins is correlated with tumor angiogenesis, we conjugated a photosensitizer (5-(4-carboxyphenyl)-10,15,20-triphenylchlorin or porphyrin) to the α_vβ₃ integrin specific peptide RGD (H-Arg-Gly-Asp-OH) motif as a common sequence. We reported an efficient solid-phase synthesis of a new family of peptidic photosensitizers with linear or cyclic[RGDfK] RGD motif and compared conjugates in vitro selectivity and photodynamic activity. The conjugates were characterized by ¹H NMR, MALDI, UV–visible spectroscopy and singlet oxygen formation was performed. Chlorins containing linear and constrained RGD motif were incorporated up to 98- and 80-fold more, respectively, than the unconjugated photosensitizer over a 24-h exposure in human umbilical vein endothelial cells (HUVEC) over-expressing α_vβ₃ integrin. Peptidic moiety also led to a non-specific increased cellular uptake by murine mammary carcinoma cells (EMT-6), lacking RGD binding receptors. Survival measurements demonstrated that HUVEC were greatly sensitive to conjugates-mediated photodynamic therapy.