DNA hydrogels could be used in drug delivery

Scientists at Cornell University have found that they can easily alter certain properties of gelatinous materials, including rigidity and absorbency, by adjusting the types of branched DNA used in them and the concentration of DNA in the mix, allowing drugs to disperse in a controlled fashion as the structure biodegrades.

Hydrogels for these purposes are usually made from organic or inorganic polymers, using organic solvents or acids or involving high temperatures, making conditions too harsh for a drug or living cells, so the materials to be encapsulated must be loaded in afterward.

The new process however, developed in the laboratory of Dan Luo, Cornell assistant professor of biological and environmental engineering, does not require high temperatures or harsh chemicals, so the material to be encapsulated in the gel can be introduced before the gel is formed.

Because the gel is made of only synthetic DNA, no immune response should be triggered, the researchers said, so the material encapsulated can include proteins and even live mammalian cells.

Hydrogels are liquid or semisolid materials composed of long-chain molecules cross-linked to one another to create many small empty spaces that can absorb water or other liquids like a sponge.

If the spaces are filled with a drug, the hydrogel can dispense the drug gradually as the structure biodegrades.

By making synthetic DNA chains whose sequences are complementary over only part of their length, Luo and colleagues have created tree-shaped structures that can be used to make hydrogels.

This is achieved by taking branched DNA and shaping it into crosses, Ys and Ts, with "sticky" ends that can link to each other with the help of enzymes known as ligases.

The cross-shaped branched DNA forms a gel by linking together into sheets of tiny squares that tangle in three dimensions; Y shapes form hexagonal structures like a chain link fence that combine into a fibrous three-dimensional form, while T shapes create random, disorganized patterns that look like an assembly of scales.

To demonstrate the ability of some of the materials to hold their shape, the researchers created them in a variety of different molds, including some that spelled out "CORNELL" at centimetre and nanoscales.

To test the use of the DNA hydrogels for delivering drugs, the researchers encapsulated porcine insulin and the anticancer drug camptothecin and observed that the drugs were released in a controlled manner over time.

The research was partially supported by the Cornell Centre for Materials Research, Cornell Centre for Advanced Technology and a National Science Foundation Early Career Development Award, and was published this week in the online version of Nature Materials​.