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Nanoscale cell adhesion ligand presentation regulates nonviral gene delivery and expression.

ABSTRACT: It is hypothesized that the nanoscale organization of cell adhesion ligands in a synthetic ECM regulates nonviral gene delivery. This hypothesis was examined with pre-osteoblasts cultured on substrates which present varied density and spacing of synthetic adhesion ligands. The levels of gene transfer and expression were increased with the density of adhesion ligands, but decreased with the spacing of ligands, due to changes in the cell growth rate. This study provides a material-based control point on the nanometer scale for nonviral gene based therapies.

SUBMITTER: Kong HJ

PROVIDER: S-EPMC2581921 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature

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Nanoscale cell adhesion ligand presentation regulates nonviral gene delivery and expression.

Kong Hyun Joon HJ Hsiong Susan S Mooney David J DJ

Nano letters 20070101 1

It is hypothesized that the nanoscale organization of cell adhesion ligands in a synthetic ECM regulates nonviral gene delivery. This hypothesis was examined with pre-osteoblasts cultured on substrates which present varied density and spacing of synthetic adhesion ligands. The levels of gene transfer and expression were increased with the density of adhesion ligands, but decreased with the spacing of ligands, due to changes in the cell growth rate. This study provides a material-based control po ...[more]

PMID: 17212457

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Project description: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.

Dataset Information

Nanoscale cell adhesion ligand presentation regulates nonviral gene delivery and expression.

Publications

Nanoscale cell adhesion ligand presentation regulates nonviral gene delivery and expression.

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