Effect and mechanism of a new photodynamic therapy with glycoconjugated fullerene.
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).
Otake
Eiko
E
Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. eaeeae107@yahoo.co.jp
Sakuma
Shiho
S
Torii
Kan
K
Maeda
Akira
A
Ohi
Hiromi
H
Yano
Shigenobu
S
Morita
Akimichi
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D037741:Fullerenes / Q000737:chemistry / Q000627:therapeutic use*; D006001:Glycoconjugates / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000627:therapeutic use*; D026082:Singlet Oxygen / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D037741:Fullerenes; D006001:Glycoconjugates; D017319:Photosensitizing Agents; D026082:Singlet Oxygen; C069837:fullerene C60