title: A phthalocyanine-peptide conjugate with high in vitro photodynamic activity and enhanced in vivo tumor-retention property.
abstract: A novel zinc(II) phthalocyanine conjugated with a short peptide with a nuclear localization sequence, Gly-Gly-Pro-Lys-Lys-Lys-Arg-Lys-Val, was synthesized by click chemistry and a standard Fmoc solid-phase peptide synthesis protocol. The conjugate was purified by HPLC and characterized with UV/Vis and high-resolution mass spectroscopic methods. Both this compound and its non-peptide-conjugated analogue are essentially non-aggregated in N,N-dimethylformamide and can generate singlet oxygen effectively with quantum yields (Φ(Δ)) of 0.84 and 0.81, respectively, relative to unsubstituted zinc(II) phthalocyanine (Φ(Δ) =0.56). Conjugation of the peptide sequence, however, can enhance the cellular uptake, efficiency in generating intracellular reactive oxygen species, and photocytotoxicity of the phthalocyanine-based photosensitizer against HT29 human colorectal carcinoma cells. The IC(50) value of the conjugate is as low as 0.21 μM. In addition, the conjugate shows an enhanced tumor-retention property in tumor-bearing nude mice. After 72 h post-injection, the dye concentration in the tumor was significantly higher than that in other organs. The results suggest that this phthalocyanine-peptide conjugate is a highly promising photosensitizer for photodynamic therapy.
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, PR China.
authors.forename: Mei-Rong
authors.initials: MR
authors.lastname: Ke
authors.forename: Sin-Lui
authors.initials: SL
authors.lastname: Yeung
authors.forename: Wing-Ping
authors.initials: WP
authors.lastname: Fong
authors.forename: Dennis K P
authors.initials: DK
authors.lastname: Ng
authors.forename: Pui-Chi
authors.initials: PC
authors.lastname: Lo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D057930:Click Chemistry; D004126:Dimethylformamide; D005559:Formamides / Q000737:chemistry*; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D054833:Isoindoles; D051379:Mice; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology*; D026082:Singlet Oxygen; D017967:Zinc Compounds
chemical_list: D005559:Formamides; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D010455:Peptides; D017319:Photosensitizing Agents; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; D026082:Singlet Oxygen; D004126:Dimethylformamide