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A Phthalocyanine–Peptide Conjugate with High In Vitro Photodynamic Activity and Enhanced In Vivo Tumor‐Retention Property
Author(s) -
Ke MeiRong,
Yeung SinLui,
Fong WingPing,
Ng Dennis K. P.,
Lo PuiChi
Publication year - 2012
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201103516
Subject(s) - photosensitizer , conjugate , singlet oxygen , phthalocyanine , peptide , chemistry , conjugated system , photodynamic therapy , in vitro , zinc , in vivo , combinatorial chemistry , photochemistry , stereochemistry , biophysics , biochemistry , organic chemistry , oxygen , biology , mathematical analysis , mathematics , microbiology and biotechnology , polymer
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 μ M . 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.