Effect and mechanism of a new photodynamic therapy with glycoconjugated fullerene.

Abstract

When irradiated, fullerene efficiently generates reactive oxygen species (ROS) and is an attractive photosensitizer for photodynamic therapy (PDT). Ideally, photosensitizers for PDT should be water-soluble and tumor-specific. Because cancer cells endocytose glucose more effectively than normal cells, the characteristics of fullerene as a photosensitizer were improved by combining it with glucose. The cytotoxicity of PDT was studied in several cancer cell lines cultured with C(60)-(Glc)1 (D-glucose residue pendant fullerene) and C(60)-(6Glc)1 (a maltohexaose residue pendant fullerene) subsequently irradiated with UVA(1). PDT alone induced significant cytotoxicity. In contrast, PDT with the glycoconjugated fullerene exhibited no significant cytotoxicity against normal fibroblasts, indicating that PDT with these compounds targeted cancer cells. To investigate whether the effects of PDT with glycoconjugated fullerene were because of the generation of singlet oxygen ((1)O(2)), NaN(3) was added to cancer cells during irradiation. NaN(3) extensively blocked PDT-induced apoptosis, suggesting that PDT-induced cell death was a result of the generation of (1)O(2). Finally, to investigate the effect of PDT in vivo, melanoma-bearing mice were injected intratumorally with C(60)-(Glc)1 and irradiated with UVA(1). PDT with C(60)-(Glc)1 suppressed tumor growth. These findings indicate that PDT with glycoconjugated fullerene exhibits tumor-specific cytotoxicity both in vivo and in vitro via the induction of (1)O(2).

• Authors: Eiko Otake, Shiho Sakuma, Kan Torii, Akira Maeda, Hiromi Ohi, Shigenobu Yano, Akimichi Morita
• Journal: Photochemistry and photobiology (Photochem Photobiol) 2010 Nov-Dec Vol. 86 Issue 6 Pg. 1356-63 ISSN: 1751-1097 [Electronic] United States
• PMID: 20796243 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 The Authors. Journal Compilation. The American Society of Photobiology.

Chemical References

• Fullerenes
• Glycoconjugates
• Photosensitizing Agents
• Singlet Oxygen
• fullerene C60

Topics

• Animals
• Apoptosis (drug effects)
• Cell Line, Tumor
• Fullerenes (chemistry, therapeutic use)
• Glycoconjugates (chemistry, therapeutic use)
• Humans
• Mice
• Mice, Nude
• Molecular Structure
• Neoplasms (drug therapy, metabolism, pathology)
• Photochemotherapy (methods)
• Photosensitizing Agents (chemistry, therapeutic use)
• Singlet Oxygen (metabolism)
• Xenograft Model Antitumor Assays