Serum albumin as a vehicle for zinc phthalocyanine: photodynamic activities in solid tumour models

• Published in: British journal of cancer Vol. 74; no. 12; pp. 1886 - 1890
• Main Authors: LARROQUE, C, PELEGRIN, A, VAN LIER, J. E
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-12-1996
• Subjects: Animals; Biological and medical sciences; Cells, Cultured; Cytochrome P-450 Enzyme System - drug effects; Drug Carriers - chemistry; Drug Delivery Systems; Female; Humans; Indoles - administration & dosage; Indoles - blood; Indoles - pharmacology; Liver - cytology; Liver - drug effects; Liver - enzymology; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasms, Experimental - drug therapy; Organometallic Compounds - administration & dosage; Organometallic Compounds - blood; Organometallic Compounds - pharmacology; Photochemotherapy - methods; Photoradiation therapy and photosensitizing agent; Photosensitizing Agents - administration & dosage; Photosensitizing Agents - blood; Photosensitizing Agents - pharmacology; Serum Albumin - chemistry; Treatment with physical agents; Treatment. General aspects; Tumors; Animal model; Carcinoma; Sarcoma; Rodentia; Zinc complex; Albumin; Malignant tumor; Photochemotherapy; Phototherapy; Colonic disease; Mammary gland diseases; Vertebrata; Mammalia; Treatment; Mouse; Metallophthalocyanine; Animal; Established cell line; Dosage form; Digestive diseases; Intestinal disease; Colon; Mammary gland; Photosensitizer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.1996.649

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.