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Water-Soluble Fullerene (C60) Derivatives as Nonviral Gene-Delivery Vectors
- Source :
- Molecular Pharmaceutics
- Publication Year :
- 2008
- Publisher :
- American Chemical Society, 2008.
-
Abstract
- A new class of water-soluble C60 transfecting agents has been prepared using Hirsch-Bingel chemistry and assessed for their ability to act as gene-delivery vectors in vitro. In an effort to elucidate the relationship between the hydrophobicity of the fullerene core, the hydrophilicity of the water-solubilizing groups, and the overall charge state of the C60 vectors in gene delivery and expression, several different C60 derivatives were synthesized to yield either positively charged, negatively charged, or neutral chemical functionalities under physiological conditions. These fullerene derivatives were then tested for their ability to transfect cells grown in culture with DNA carrying the green fluorescent protein (GFP) reporter gene. Statistically significant expression of GFP was observed for all forms of the C60 derivatives when used as DNA vectors and compared to the ability of naked DNA alone to transfect cells. However, efficient in vitro transfection was only achieved with the two positively charged C60 derivatives, namely, an octa-amino derivatized C60 and a dodeca-amino derivatized C60 vector. All C60 vectors showed an increase in toxicity in a dose-dependent manner. Increased levels of cellular toxicity were observed for positively charged C60 vectors relative to the negatively charged and neutral vectors. Structural analyses using dynamic light scattering and optical microscopy offered further insights into possible correlations between the various derivatized C60 compounds, the C60 vector/DNA complexes, their physical attributes (aggregation, charge) and their transfection efficiencies. Recently, similar Gd@C60-based compounds have demonstrated potential as advanced contrast agents for magnetic resonance imaging (MRI). Thus, the successful demonstration of intracellular DNA uptake, intracellular transport, and gene expression from DNA using C60 vectors suggests the possibility of developing analogous Gd@C60-based vectors to serve simultaneously as both therapeutic and diagnostic agents.
- Subjects :
- Cell Survival
gene transfection
Genetic Vectors
Pharmaceutical Science
02 engineering and technology
Gene delivery
Biology
010402 general chemistry
01 natural sciences
Article
Green fluorescent protein
Cell Line
chemistry.chemical_compound
Mice
Drug Discovery
Animals
Vector (molecular biology)
Transgenes
nonviral vector
Reporter gene
Molecular Structure
fullerenes
Water
Transfection
DNA
021001 nanoscience & nanotechnology
Molecular biology
0104 chemical sciences
C60
chemistry
Solubility
Cell culture
Naked DNA
Viruses
Biophysics
Molecular Medicine
cytotoxicity
0210 nano-technology
Subjects
Details
- Language :
- English
- ISSN :
- 15438392 and 15438384
- Volume :
- 5
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Molecular Pharmaceutics
- Accession number :
- edsair.doi.dedup.....5b2611b5e31acfe26c9862bada5c44fc