DNA Buckyballs for Drug Delivery - Use of Synthetic DNA as Building Blocks

DNA isn't just for storing genetic codes any more. Since DNA can polymerize -- linking many molecules together into larger structures -- scientists have been using it as a nanoscale building material, constructing geometric shapes and even working mechanical devices.

Now Cornell University researchers have made DNA buckyballs -- tiny geodesic spheres that could be used for drug delivery and as containers for chemical reactions.

A scanning electron microscope image of a self-assembled DNA buckyball.

The term "buckyballs" has been used up to now for tiny spherical assemblies of carbon atoms known as Buckminsterfullerenes or just fullerenes. Under the right conditions, carbon atoms can link up into hexagons and pentagons, which in turn assemble into spherical shapes (technically truncated icosahedrons) resembling the geodesic domes designed by the architect-engineer Buckminster Fuller. Instead of carbon, the Cornell researchers are making buckyballs out of a specially prepared, branched DNA-polystyrene hybrid. The hybrid molecules spontaneously self-assemble into hollow balls about 400 nanometers (nm) in diameter. The DNA/polystyrene "rods" forming the structure are each about 15 nm long. (While still on the nanoscale, the DNA spheres are much larger than carbon buckyballs, which are typically around 7 nm in diameter.)

About 70 percent of the volume of the DNA buckyball is hollow, and the open spaces in the structure allow water to enter. The researchers believe that drugs could be encapsulated in buckyballs to be carried into cells, where natural enzymes would break down the DNA, releasing the drug.

The nanoscale, hollow buckyballs are also the first structures assembled from "dendrimerlike DNA." If three strands of artificial DNA are created such that portions of each strand are complementary to portions of another, the three strands will bind to each other over the complementary portions, creating a Y-shaped molecule. By joining several Y's in the same way, the research group created molecules with several arms, a sort of tree shape (dendri- means tree in Greek). Then they attached polystyrene molecules to the dendrimerlike DNA, forming a hybrid molecule called an amphiphile -- a molecule that both likes and hates water. DNA is hydrophillic -- attracted to water -- while polystyrene is hydrophobic -- water repels it.

The researchers expected the amphiphiles to assemble in water into some sort of solid structure arranged so that DNA would have a maximum interaction with water and polystyrene would avoid water as much as possible. Other researchers have used other amphiphiles to make spheres, rods and other solids. The hollow buckyballs were an intriguing and serendipitous surprise. A model suggests that one buckyball consists of about 19,000 amphiphiles, with their water-loving DNA mostly on the outside of the rods that form the structure. According to the researchers, how these tens of thousands of molecules were able to self-organize to form such an intricate and complex structure is still an open question. They are seeking collaborators to solve the puzzle.

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