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Photodynamic activity of BAM‐SiPc, an unsymmetrical bisamino silicon(IV) phthalocyanine, in tumour‐bearing nude mice
Author(s) -
Leung S C H,
Lo PC,
Ng D K P,
Liu WK,
Fung KP,
Fong WP
Publication year - 2008
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/bjp.2008.82
Subject(s) - photodynamic therapy , in vivo , phototoxicity , cancer research , chemistry , in vitro , phthalocyanine , biodistribution , cell culture , apoptosis , cell , cancer , pharmacology , biochemistry , medicine , biology , genetics , microbiology and biotechnology , organic chemistry
Background and purpose: Ever since the discovery of photodynamic therapy, there has been a continuous search for more potent photosensitizers. Towards that end, we have synthesized a number of novel phthalocyanine derivatives. The unsymmetrical bisamino silicon(IV) phthalocyanine BAM‐SiPc is one of the most potent compounds. In in vitro cell culture, it exhibits high phototoxicity against a number of cancer cell lines. Experimental approach: In the present investigation, the in vivo effect of BAM‐SiPc was studied in the tumour‐bearing nude mice model. The biodistribution of BAM‐SiPc was followed to evaluate its tumour selectivity and rate of clearance. The tumour volume in the hepatocarcinoma HepG2‐ and the colorectal adenocarcinoma HT29‐bearing nude mice was measured after photodynamic therapy. The level of intrinsic toxicity induced was also investigated. Finally, the metabolism of BAM‐SiPc in the ‘normal’ WRL68 liver cells and the hepatocarcinoma HepG2 cells was compared. Key results: The results not only showed significant tumour regression of HepG2 and growth inhibition of HT29 in the tumour‐bearing nude mice, but also no apparent hepatic or cardiac injury with the protocol used. Histological analyses showed that apoptosis was induced in the solid tumour. BAM‐SiPc could be metabolized by WRL68 liver cells but not by the hepatocarcinoma HepG2 cells. Unfortunately, BAM‐SiPc did not show any specific targeting towards the tumour tissue. Conclusions and implications: The efficiency of BAM‐SiPc in inhibiting tumour growth makes it a good candidate for further evaluation. Enhancement of its uptake in tumour tissue by conjugation with biomolecules is currently under investigation.