Hexa(sulfobuty)fullerene-induced Photodynamic Effect on Tumors in Vivo and Toxicity Study in Rats

摘要

Highly water-soluble hexa(sulfobutyl)fullerenes (FC_4S) were synthesized in ayield of 80-85percent by the treatment of C_(60) in dimethoxyethane (DME) with sodium naphthalide (10.0 equiv.) at 25 deg C, followed by reacting the resulting hexaanionic fullerene intermediates with an excess of 1,4-butane sultone (15.0 equiv.). The medium lethal dose (LD_(50)) of FC_4S was defined as approximately600 mg/kg in acute toxicity studies. No adverse effect was noted in the animals when the uptake of FC_4S was made orlaly. Limit toxicity on kidney cells was revealed in experiments with intraperitoneal administration of FC_4S in multiple doses with a dose level of 60 mg/kg each, showing decrease in body weight and morphologic effects of phagolysosomal nephrophyathy in rats. A similar degree of toxicity was observed in experiments with a single dose of FC_4S by intravenous injection at 100 mg/kg. Despite of morphologic changes of kdeney cells, no obvious adverse reaction on blood chemistry in kidney and other organs was observed. The ICR mice implanted with sarcoma 180 tumor cells on the subcuticle skin area was utilized as an animal model. Upon administration of FC_4S (15 mg/kg) by intraperitoneal injection and the photodynamic treatment on the tumor-bearing mouse using argon laser irradiation at 514.5 nm with the total light dose of 100 J/cm~2, the tumor size was found to decrease largely to only roughly 10percent of the tumor control at 30 days after laser irradation. These data substantiated the effectiveness of FC_4S in reducing the growth of tumor in vivo and demonstrate the potential use of it as a sensitizing agent in the photodynamic therapy for the tumor and cancer related diseases.