Photodynamic activity of BAM-SiPc, an unsymmetrical bisamino silicon(IV) phthalocyanine, in tumour-bearing nude mice.
OBJECTIVE
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.


METHODS
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.


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
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.
Leung
S C H
SC
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Lo
P-C
PC
Ng
D K P
DK
Liu
W-K
WK
Fung
K-P
KP
Fong
W-P
WP
D000818:Animals; D045744:Cell Line, Tumor; D019073:HT29 Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D007211:Indoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D017646:Organosilicon Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution
C516359:BAM-SiPc; D007211:Indoles; D017646:Organosilicon Compounds; D017319:Photosensitizing Agents