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.
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Authors | Mei-Rong Ke, Sin-Lui Yeung, Wing-Ping Fong, Dennis K P Ng, Pui-Chi Lo |
Journal | Chemistry (Weinheim an der Bergstrasse, Germany)
(Chemistry)
Vol. 18
Issue 14
Pg. 4225-33
(Apr 02 2012)
ISSN: 1521-3765 [Electronic] Germany |
PMID | 22378352
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 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
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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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