title: Synthesis and in vitro photodynamic activities of an integrin-targeting cRGD-conjugated zinc(II) phthalocyanine.
abstract: A 1,4-disubstituted zinc(II) phthalocyanine conjugated with a cyclic Arg-Gly-Asp-D-Phe-Lys (cRGDfK) moiety through a triazole linker was prepared and characterized by UV/Vis spectroscopy and high-resolution ESI-MS. The conjugate showed a relatively weak fluorescence emission in N,N-dimethylformamide (ΦF =0.08), but it was a very efficient singlet oxygen generator (ΦΔ=0.80) as a result of the di-α-substituted structure. Owing to the presence of the cyclic peptide sequence cRGDfK, which is a well-known αvβ3 -integrin antagonist, this conjugate exhibited significantly higher cellular uptake toward the αvβ3(+) U87-MG cells compared with the αvβ3(-) MCF-7 cells, as determined by flow cytometry and fluorescence microscopy. The photocytotoxicity of this compound against these two cell lines, however, was comparable owing to the similar efficiency of intracellular reactive oxygen species generation. Confocal microscopic studies also revealed that this conjugate localized preferentially in the lysosomes, but not in the nucleus, endoplasmic reticulum, and mitochondria of the U87-MG cells.
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong (S.A.R. China), Fax: (+852) 2603 5057.
authors.forename: Mei-Rong
authors.initials: MR
authors.lastname: Ke
authors.forename: Dennis K P
authors.initials: DK
authors.lastname: Ng
authors.forename: Pui-Chi
authors.initials: PC
authors.lastname: Lo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054833:Isoindoles; D061986:MCF-7 Cells; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000188:drug therapy; D009842:Oligopeptides / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000627:therapeutic use / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D017967:Zinc Compounds
chemical_list: D056831:Coordination Complexes; D007211:Indoles; D016023:Integrins; D054833:Isoindoles; D009842:Oligopeptides; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; C047981:arginyl-glycyl-aspartic acid
keywords: imaging agents; peptides; photochemistry; phthalocyanines; sensitizers