title: Cytotoxicity and TNF-alpha secretion in RAW264.7 macrophages exposed to different fullerene derivatives.
abstract: Fullerene derivatives have been reported as potential nanomedicines, however the role of surface chemical modification on the biological effects remains unclear. In this study, five kinds of water soluble C60 derivatives with different surface chemical modification, C60-(OH)20 (HFD), C60-(beta-Ala)10.1 (AFD), C60-(Lys)8.7 (KFD), C60-(Arg)8.6 (RFD) and C60-(NH(CH2)2NH2)8.8 (NFD) were synthesized. Their cytotoxicity as well as TNF-alpha secretions were evaluated in RAW264.7 macrophage cell line. The results show that no significant cytotoxicity can be observed upon 24 h exposure to C60 derivatives at less than 50 microg/mL. However, higher concentration (> 100 microg/mL) of these C60 derivatives decreases the proliferation of RAW264.7. The cytotoxicity of these fullerene derivatives is probably through the apoptosis pathway, while the extent of cytotoxicity varies with the different surface charges. Higher celluar uptake of HFD was observed in RAW264.7 cells than AFD, which correlates with the more toxic effect of HFD over AFD. The secretion of cytokine tumor necrosis factor alpha (TNF-alpha) was determined to evaluate the immunostimulating activity of these fullerene derivatives. The data show that the fullerene derivatives with negative surface charges secrete more TNF-alpha, whereas derivatives with positive charges show insignificant effect. The possible influence of various surface charge property on the observed biological effects is discussed.
authors: Beijing National Laboratory for Molecular Sciences, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, PR China.
authors: Kun
authors: K
authors: Xiang
authors: Zengpei
authors: Z
authors: Dou
authors: Yuankai
authors: Y
authors: Li
authors: Yingying
authors: Y
authors: Xu
authors: Jiadan
authors: J
authors: Zhu
authors: Shengtao
authors: S
authors: Yang
authors: Hongfang
authors: H
authors: Sun
authors: Yuanfang
authors: Y
authors: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D037741:Fullerenes / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D037741:Fullerenes; D014409:Tumor Necrosis Factor-alpha