DNA nanostructures pave the way for functional delivery vectors of drugs

A new study shows that nanostructures composed of DNA molecules can be programmed to function as pH-sensitive cargo carriers, thus opening the way for functional drug delivery vehicles.

Researchers from the University of Jyväskylä and the Aalto University in Finland have developed a customized DNA nanostructure that can perform a predefined task under conditions similar to those of the human body. To do this, the team has built a capsule-shaped holder that opens and closes according to the pH level of the surrounding solution. The nanocapsule can be loaded – or packaged – with a variety of cargoes, closed for delivery and reopened through a subtle increase in pH.
The function of the DNA nanocapsule is based on pH sensitive DNA residues.

To do this, the team designed a capsule-like DNA origami structure, functionalized with pH-sensitive DNA strands. These dynamic DNA nanodesigns are often controlled by the simple hydrogen bonding of two complementary DNA sequences. Here, one half of the capsule was equipped with specific domains of double-stranded DNA that could form a triple helix of DNA – in other words, a helical structure made up of three, not just two molecules of DNA – by binding to a single-stranded DNA in the other half.

"Triplex formation can occur only when the surrounding pH of the solution is correct. We call these pH-sensitive strands "pH locks" because when the strands interact, they work similarly to their macroscopic counterparts and lock the capsule in a closed state. We have included several motifs in the design of our capsule to facilitate the opening / closing of the capsule according to the cooperative behavior of the locks. The opening of the capsule is actually very fast and only requires a slight increase in the pH of the solution, "says the first author of the study, PhD student Heini Ijäs of the Nanoscience Center of the University of Jyväskylä ..

Nanoparticles and enzymes could be loaded and encapsulated in capsules

To exploit the nanocapsules intended for the transport of molecular payloads or therapeutic substances, the team designed the capsule with a cavity that can accommodate different materials. They demonstrated that gold nanoparticles and enzymes could be loaded (high pH) and encapsulated in capsules (low pH) and again displayed (high pH). By monitoring the activity of the enzyme, the researchers found that the cargo remained fully functional during the process.

"The most intriguing thing about DNA origami capsules is that the pH threshold at which the opening and closing takes place is fully adjustable by selecting the basic sequences of the pH locks. We designed the pH threshold of 7.2 to 7.3, close to blood pH. In the future, this type of drug vector could be optimized to open selectively inside specific cancer cells, which can maintain a higher pH than healthy cells. " Veikko Linko, Adjunct Professor at Aalto University.

In addition, the capsules remained functional at physiological concentrations of magnesium and sodium and in 10% blood plasma, and can continue to do so at even higher plasma concentrations. Together, these results help pave the way for the development of intelligent, fully programmable drug delivery vehicles for nanomedicine.