Journal
PHOTOCHEMISTRY AND PHOTOBIOLOGY
Volume 86, Issue 6, Pages 1356-1363Publisher
WILEY
DOI: 10.1111/j.1751-1097.2010.00790.x
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology, Japan
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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 (1O(2)), NaN3 was added to cancer cells during irradiation. NaN3 extensively blocked PDT-induced apoptosis, suggesting that PDT-induced cell death was a result of the generation of 1O(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 1O(2).
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