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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.
AuthorsMei-Rong Ke, Sin-Lui Yeung, Wing-Ping Fong, Dennis K P Ng, Pui-Chi Lo
JournalChemistry (Weinheim an der Bergstrasse, Germany) (Chemistry) Vol. 18 Issue 14 Pg. 4225-33 (Apr 02 2012) ISSN: 1521-3765 [Electronic] Germany
PMID22378352 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Chemical References
  • Formamides
  • Indoles
  • Isoindoles
  • Organometallic Compounds
  • Peptides
  • Photosensitizing Agents
  • Zinc Compounds
  • Zn(II)-phthalocyanine
  • Singlet Oxygen
  • Dimethylformamide
Topics
  • Amino Acid Sequence
  • Animals
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Click Chemistry
  • Dimethylformamide
  • Formamides (chemistry)
  • Humans
  • Indoles (chemistry, pharmacology)
  • Isoindoles
  • Mice
  • Organometallic Compounds (chemistry, pharmacology)
  • Peptides (chemistry)
  • Photochemotherapy
  • Photosensitizing Agents (chemistry, pharmacology)
  • Singlet Oxygen
  • Zinc Compounds

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