In vivo gene delivery by cationic tetraamino fullerene

Abstract

Application of nanotechnology to medical biology has brought remarkable success. Water-soluble fullerenes are molecules with great potential for biological use because they can endow unique characteristics of amphipathic property and form a self-assembled structure by chemical modification. Effective gene delivery in vitro with tetra(piperazino)fullerene epoxide (TPFE) and its superiority to Lipofectin have been described in a previous report. For this study, we evaluated the efficacy of in vivo gene delivery by TPFE. Delivery of enhanced green fluorescent protein gene (EGFP) by TPFE on pregnant female ICR mice showed distinct organ selectivity compared with Lipofectin; moreover, higher gene expression by TPFE was found in liver and spleen, but not in the lung. No acute toxicity of TPFE was found for the liver and kidney, although Lipofectin significantly increased liver enzymes and blood urea nitrogen. In fetal tissues, neither TPFE nor Lipofectin induced EGFP gene expression. Delivery of insulin 2 gene to female C57/BL6 mice increased plasma insulin levels and reduced blood glucose concentrations, indicating the potential of TPFE-based gene delivery for clinical application. In conclusion, this study demonstrated effective gene delivery in vivo for the first time using a water-soluble fullerene.

Evidence for nuclear internalisation of biocompatible [60]fullerene1)

“…This observation is consistent with the fact that a similar unlabelled compound, C 60 -ser (12) , can be used as a transfection agent (13) , as can other C 60 derivatives, both in vitro (14) and in vivo (15) . The C 60 -serPF conjugate is non-cytotoxic at the doses examined here ( ≤ 0.1 mg mL 1 ) for HeLa (cervical cancer), SNU449 (liver cancer), SKOV3 (ovarian cancer), and HEK293T (immortalised fibroblast) cells.…”

Therapeutic applications of low-toxicity spherical nanocarbon materials

“…In particular, manufactured nanocarbon materials, including fullerenes, carbon nanotubes, carbon nanohorns and graphene, have been shown to be extremely useful in various biology-related applications such as nanomedicine, drug delivery and biolabeling. [8][9][10][11][12] For example, Nakamura et al 13,14 recently described how functionalized fullerenes could be used to deliver the green fluorescent protein gene in vitro and in vivo; higher gene expression was found in the liver and spleen. This research points toward the possible application of fullerenes as novel agents for gene therapy.…”

Fullerene–biomolecule conjugates and their biomedicinal applications

“…The membranotropic characteristics of fullerenes also have profound implications in the development of various cationic two-handed aminofullerenes for drug delivery, particularly in the field of gene delivery [55][56][57] or peptide transport. 11,58 It was concluded that fullerene amino acids and fullerenepeptide play important roles in providing safe, hydrophobic Two previous studies have suggested utilizing the membranotropic characteristics of fullerenes to treat hypoxia-induced mitochondrial dysfunction in mammalian heart myocytes.…”