Traceable Nanocarriers Pinpoint Delivery of Gene Therapy Reagents

The polycation structures contained repeated oligoethyleneamines, for binding and compacting nucleic acids, and lanthanide (Ln) chelates (either luminescent europium or paramagnetic gadolinium). The chelated Lns allowed the visualization of the nanoparticles both via microscopy and magnetic resonance imaging (MRI).

Results of studies to evaluate the properties of the nanocarriers were published in the October 6, 2009, issue of the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS). They showed that plasmid (p)DNA was effectively bound and compacted into the nanoparticles, which protected the nucleic acids from nuclease damage. These nanocarriers efficiently delivered pDNA into cultured cells and did not exhibit toxicity.

Micrographs of cultured cells exposed to the nanoparticle complexes formed with fluorescein-labeled pDNA and the europium-chelated polymers revealed effective intracellular imaging of the delivery process. MRI of bulk cells exposed to the complexes formulated with pDNA and the gadolinium-chelated structures showed bright image contrast, allowing visualization of effective intracellular delivery on the tissue-scale.

"My lab has been trying to find a way to deliver genetic-based drugs into cells," said senior author Dr. Theresa M. Reineke, associate professor of chemistry at Virginia Polytechnic Institute. "Traditional drugs are aimed at treating disease at the protein level. Genetic drugs – such as those that can alter or control gene expression – aim to treat disease at the genetic level and have the added benefit of being more specific for their medicinal target."

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