(Photo : Veikko Linko, Boxuan Shen and Heini Ijäs/Aalto University)

The nanostructures constructed of DNA molecules can be programmed to function at pH-responsive cargo carriers, paving the way towards functional drug-delivery vehicles, according to a new study of the University of Jyvaskyla and Aalto University.

University of Jyvaskyla and Aalto University's researchers have developed a customized DNA nanostructure that can perform a predefined task in human body-like conditions. To do so, the group built a capsule-like carrier that opens and closes according to the pH level of the surrounding solution. Now, it is possible to load and pack the nanocapsule with a variety of cargo, closed for delivery and opened again through a subtle pH increase. The function of the DNA nanocapsule has a basis on pH-responsive DNA residues.

To this end, this team of researchers designed a capsule-like DNA origami structure functionalized with pH-responsive DNA strands. The simple hydrogen-bonding of two complementary DNA sequences controls such dynamic DNA nano designs. Here, one half of the capsule was equipped with specific double-stranded DNA domains that could further form a DNA triple helix, in other words, a helical structure comprised of three, not just two DNA molecules, by attaching to a suitable single-stranded DNA in the other half.

The lead author of the study explained that when the surrounding pH of the solution is right, the triplex formation can happen. Scientists call these pH-responsive strands "pH latches" because when the strands interact, they function similar to their macroscopic counterparts and lock the capsule in a closed state. Also included are the various motifs into the capsule design to facilitate the capsule opening and closing based on the cooperative behavior of the latches. The opening of the capsule is indeed quite rapid and requires only a slight pH increase in the solution. And within the capsules, it is easy to load the nanoparticles and enzymes.

The team tied the nanocapsules for carrying molecular payloads or therapeutic substances by designing the capsule with a cavity that could not host different materials. Also, the team demonstrated that both gold nanoparticles and enzymes could be loaded (high pH) and encapsulated within the capsules (low pH) and again displayed (high pH). While monitoring the enzyme activity, the researchers discovered that the cargo remained fully functional throughout the process.

Ultimately, the capsules continued to be effective at physiological magnesium and sodium concentrations, and in ten percent blood plasma, and may continue to do at even higher plasma concentrations. Together, these discoveries help pave the way for developing smart and fully programmable drug-delivery vehicles for nanomedicine.