Photodynamic Effect of Polyethylene Glycol–modified Fullerene on Tumor

Abstract

Fullerene (Cm) efficiently generates singlet oxygen when irradiated with light, and thus should have a photodynamic effect on tumors, if it is accumulated in the tumor tissue. To explore tumor targeting of CU, we chemically modified the water–insoluble C60 with polyethylene glycol (PEG), not only to make it soluble in water, but also to enlarge its molecular size. When injected intravenously into mice carrying a tumor mass in the hack sulicutis, the C60–PEG conjugate exhibited higher accumulation and more prolonged retention in the tumor tissue than in normal tissue. The conjugate was excreted without being accumulated in any specific organ. Following intravenous injection of CorPEG conjugate or Photofrin® to tumor–bearing mice, coupled with exposure of the tumor site to visible light, the volume increase of the tumor mass was suppressed and the C60 conjugate exhibited a stronger suppressive effect than Photofrin. Histological examination revealed that conjugate injection plus light irradiation strongly induced tumor necrosis without any damage to the overlying normal skin. The antitumor effect of the conjugate increased with increasing irradiation power and Cm dose, and cures were achieved by treatment with a dose of 424 μg/kg at an irradiation power of 107 J/cm2. These findings indicate that PEG–modified cm is a candidate agent for photodynamic tumor therapy.

Metallofullerene nanoparticles circumvent tumor resistance to cisplatin by reactivating endocytosis

“…Fullerene molecules, the third form of pure carbon in addition to the diamond and graphite forms, have attracted much attention to their biomedical applications (17). It has been demonstrated that fullerenes can generate singlet oxygen and suppress tumor growth without damage to normal skin of the mice exposed to visible light (18). We have found that metallofullerene nanoparticles penetrate plasma membrane of tumor cells and result, to some degree, in shrinkage of solid tumors in vivo (19,20).…”

Syntheses and characterization of water‐soluble C60–curdlan sulfates for biological applications

“…The presence of sp 3 hybridized carbons at d ¼ 94 ppm indicated that products 1aN3SF-1cN3SF and 2aN3SF-2cN3SF possessed a [6,6]-closed structure. The absence of sp 3 hybridized C 60 resonances at d > 84 in the 13 C NMR spectra of series 1aNSF-1cNSF and series 2aNSF-2cNSF accounted for an open [5,6]-azabridged structure.…”

“…It is a thermogellable polysaccharide consisting of (b-1,3)-linked glucose residues, which can be subjected to partial sulfonation or persulfonation to yield soluble curdlan sulfate with specific biological activities. There are two main reasons that curdlan sulfate is of particular interest for fullerene chemistry: (1) depending on the degree of substitution, a series of C 60 -substituted curdlan sulfates with adequate water solubility for prospective photodynamic therapeutic agents [5][6][7][8] can be prepared, and (2) curdlan sulfates exhibit strong anti-HIV activity (EC 50 ¼ 0.04-3.08 lg mL À1 ) 9 and can act as delivery carriers of cationic-fullerene-based AIDS drugs 10 to the lymphoid tissues.…”

Intraperitoneal photodynamic therapy mediated by a fullerene in a mouse model of abdominal dissemination of colon adenocarcinoma

“…Tabata et al reported (44) in 1997 that a C 60 -PEG conjugate injected intravenously into mice carrying a subcutaneous tumor followed by exposure of the tumor site to visible light exhibited a stronger suppressive effect than Photofrin. Liu et al (45) prepared C 60 -PEG attached to DTPA-Gd and carried PDT out MRI imaging and PDT of subcutaneous tumor s using 500-500-nm light.…”