Photodynamic anti-cancer effects of fullerene [C₆₀]-PEG complex on fibrosarcomas preferentially over normal fibroblasts in terms of fullerene uptake and cytotoxicity.
A water-soluble complex of fullerene [C60]:polyethylene glycol (PEG) (1:350 wt/wt) (C60-PEG), but not PEG alone, was found in the present study by ESR/DMPO spin-trap method to generate hydroxyl radicals 6.5-fold as abundant as the non-irradiation level, when irradiated with visible light (400-600 nm, 140 J/cm(2): 450-fold as intense as in average outdoor), but not to generate without irradiation. At 3 h after irradiation with C60-PEG, human fibrosarcoma cells HT1080 were obviously degenerated together with diminished microvilli, cell shrinkage and cell fragmentation as observed by SEM and were shown either for increased cytotoxicity by dual stains with calcein-AM and propidium iodide or for nuclear condensation and fragmentation by Hoechst 33342 stain, any of which were, in contrast, scarcely changed in normal human fibroblastic cells DUMS16 derived from the same connective tissue type as HT1080 cells. Under the conditions, the maximum intracellular uptake amount was more abundant for HT1080 cells than for DUMS16 cells, either by immunostain/fluorography using polyclonal antibody against fullerene [C60], or by HPLC method indicating the 2.4-fold preferential uptake of C60-PEG into HT1080 cells, suggested to greater phagocytotic ability characteristic of cancer cells, over DUMS16 cells being non-macrophage-like normal cells. Thus, C60-PEG is expected as a photosensitizer for photodynamic therapy with scarce side effects to normal cells and preferential reactive oxygen species generation in cancer cells.
Faculty of Health Sciences, Butsuryo College of Osaka, 3-33 Otorikita-cho, Nishi-ku, Sakai, 593-8328, Japan, asada@butsuryo.ac.jp.
Ryoko
R
Asada
Feng
F
Liao
Yasukazu
Y
Saitoh
Nobuhiko
N
Miwa
D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000528:radiation effects; D005354:Fibrosarcoma / Q000473:pathology / Q000628:therapy*; D037741:Fullerenes / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D008027:Light; D010778:Photochemotherapy; D010787:Photosensitivity Disorders / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism
D037741:Fullerenes; D017382:Reactive Oxygen Species; D011092:Polyethylene Glycols