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).

Chemically modified fullerene derivatives as photosensitizers in photodynamic therapy: A first‐principles study

“…Fullerenes are a class of closed-cage nanomaterials made solely from carbon atoms. Since photoinduced biochemical activity of fullerene carboxylic acid was first reported in 1993, [6] much scientific attention has been paid to the biological activity of fullerene derivatives [7][8][9][10][11] where their main biological applications include inhibiting the human immunodeficiency virus (HIV-1) protease, using potential anticancer agent, PS, and so forth. Especially, it has been systematically reviewed that the organically modified fullerene derivatives, as promising PSs are applied in PDT.…”

Syntheses and photodynamic properties of glucopyranoside-conjugated indium(III) porphyrins as a bifunctional agent

“…For this purpose, the porphyrin and phthalocyanine derivatives having carboxylate or polyethyleneglycol groups were synthesized [14][15][16][17][18]. Yano and coworkers reported that glucopyranoside-conjugated porphyrin, chlorin and fullerene derivatives efficiently work as photosensitizers [19][20][21][22][23][24][25]. It is known that tumor has a property to accumulate glucose to the greater extent than normal tissue for the unnatural growth.…”

Preparation and characterization of injectable Mitoxantrone poly (lactic acid)/fullerene implants for in vivo chemo-photodynamic therapy

“…Furthermore, compared with radiotherapy, the activating light is non-ionizing and hence its effect on tissues without PS drug is not harmful [1][2][3]. Fullerene (C60), the third allotrope of carbon, are nano-scale carbon materials with unique photo-, electro-chemical, physical properties and low systemic toxicity [4][5][6][7]. In addition, C60 possess unique photochemical properties: under the irradiation of UV or visible light, C60 molecule is able to shift to the excitation triplet state and generate singlet and other active forms of oxygen [8,9].…”