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Nanoscale DNA Cages for Directed Delivery of Small Drug Compounds

By BiotechDaily International staff writers
Posted on 12 Sep 2013
Image: A DNA cage (at left), with lipid-like molecules (in blue). The lipids come together in a "handshake" within the cage (center image) to encapsulate small-molecule drugs (purple). The molecules are released (at right) in response to the presence of a specific nucleic acid (Photo courtesy of Thomas Edwardson, McGill University).
Image: A DNA cage (at left), with lipid-like molecules (in blue). The lipids come together in a "handshake" within the cage (center image) to encapsulate small-molecule drugs (purple). The molecules are released (at right) in response to the presence of a specific nucleic acid (Photo courtesy of Thomas Edwardson, McGill University).
A novel method for directed drug delivery is based on enclosing low molecular weight compounds in nanoscale "cages" built of DNA strands that sequester the compound until contact with a specific nucleic acid sequence triggers release of the drug.

Investigators at McGill University (Montreal, Canada) had shown previously that drugs could be loaded into gold nanoparticles that could be inserted and released from DNA nanotubes. In the current study, they greatly reduced the size of the carrier DNA constructs. Highly branched alkyl-DNA conjugates were hybridized to the edges of a DNA cube. When four amphiphiles were on one face, the hydrophobic residues of two neighboring cubes engaged in an intermolecular "handshake,” resulting in a dimer. When there were eight amphiphiles (four on the top and bottom cube faces, respectively), they engaged in an intramolecular "handshake" inside the cube. The DNA cube thus surrounded a lipid-like space into which small molecule compounds could be loaded.

Details of the construction and testing of DNA "nanocages" were published in the September 1, 2013, online edition of the journal Nature Chemistry. This paper described the creation of a three-dimensional pattern of hydrophobic patches, like side chains in proteins, which resulted in the specific, directed association of hydrophobic domains with orthogonal interactions to DNA base pairing. This formed the first example of a monodisperse micelle within a DNA nanostructure that encapsulated small molecules and released them by DNA recognition.

"This research is important for drug delivery, but also for fundamental structural biology and nanotechnology," said senior author Dr. Hanadi Sleiman, professor of chemistry at McGill University.

The investigators are now conducting cell and animal studies to assess the viability of this method on chronic lymphocytic leukemia (CLL) and prostate cancer.

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