The in vivo efficacy of phthalocyanine-nanoparticle conjugates for the photodynamic therapy of amelanotic melanoma.

Abstract

The efficiency of a Zn(II)-phthalocyanine disulphide (C11Pc), a compound with both phthalocyanine units bearing seven hexyl chains and a sulphur terminated C11 chain, as a photodynamic therapy (PDT) agent was investigated in C57 mice bearing a sub-cutaneously transplanted amelanotic melanoma. The phthalocyanine was intravenously injected at a dose of 1.5 micromol/kg body weight either free or bound to gold nanoparticles, using a Cremophor emulsion as a delivery vehicle. Biodistribution studies at selected post-injection times showed that the nanoparticle-associated C11Pc was recovered in significantly larger amounts from all the examined tissues and the serum and yielded a greater selectivity of tumour targeting: thus, the ratio between the amount of phthalocyanine recovered from the amelanotic melanoma and the skin (peritumoural tissue) increased from 2.3 to 5.5 from the free to the gold nanoparticle-bound C11Pc at 24 h after injection. PDT studies with the C11Pc-loaded amelanotic melanoma showed a markedly more significant response of the tumour in the mice that had received the nanoparticle-bound photosensitiser; the PDT effect was especially extensive if the irradiation was performed at 3h after C11Pc injection when large phthalocyanine amounts were still present in the serum. This suggests that the PDT promoted by C11Pc predominantly acts via vascular damage at least in this specific animal model. This hypothesis was fully confirmed by electron microscopy observations of tumour specimens obtained at different times after the end of PDT, showing an extensive damage of the blood capillaries and the endothelial cells.

• Authors: Monica Camerin, Michela Magaraggia, Marina Soncin, Giulio Jori, Miguel Moreno, Isabelle Chambrier, Michael J Cook, David A Russell
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 46 Issue 10 Pg. 1910-8 (Jul 2010) ISSN: 1879-0852 [Electronic] England
• PMID: 20356732 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Indoles
• Isoindoles
• Organometallic Compounds
• Photosensitizing Agents
• Zinc Compounds
• Zn(II)-phthalocyanine

Topics

• Animals
• Female
• Indoles (pharmacokinetics, therapeutic use)
• Isoindoles
• Melanoma, Amelanotic (drug therapy, pathology)
• Metal Nanoparticles (therapeutic use)
• Mice
• Mice, Inbred C57BL
• Neoplasm Transplantation
• Organometallic Compounds (pharmacokinetics, therapeutic use)
• Photochemotherapy (methods)
• Photosensitizing Agents (pharmacokinetics, therapeutic use)
• Skin Neoplasms (drug therapy, pathology)
• Zinc Compounds