Serum albumin as a vehicle for zinc phthalocyanine: photodynamic activities in solid tumour models.
Zinc phthalocyanine (ZnPc) is a second-generation photosensitiser for the photodynamic therapy (PDT) of cancer. Unsubstituted ZnPc is, however, highly insoluble in most common solvents, and for clinical applications the material needs to be incorporated in liposomes. We report a simple, alternative procedure to formulate ZnPc through non-covalent binding to bovine serum albumin (BSA). Intravenous administration of ZnPc-BSA preparations, at a molar ratio of 11:1 and at a ZnPc dose equivalent to 0.5 mol kg-1, to tumour-bearing mice followed 24 h later by PDT was shown to provide tumour control in two different models, the EMT-6 tumour in Balb/c mice and the human colon T380 carcinoma in nude mice. Analysis of serum fractions from treated animals showed that ZnPc readily redistributes over the serum high-density lipoprotein (HDL) fraction. We also demonstrated the absence of hepatic toxicity of the ZnPc-BSA preparation by monitoring the hepatic cytochrome P450 activity in treated animals and the viability of human cultured hepatocytes.
Larroque
C
C
MRC Group in the Radiation Sciences, Faculty of Medicine, Université de Sherbrooke, Québec, Canada.
Pelegrin
A
A
Van Lier
J E
JE
D000818:Animals; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D054833:Isoindoles; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D012709:Serum Albumin / Q000737:chemistry*; D017967:Zinc Compounds
D004337:Drug Carriers; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D012709:Serum Albumin; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; D003577:Cytochrome P-450 Enzyme System