A customized DNA nanostructure that can perform a predefined task in human body-like conditions has been developed by researchers from the University of Jyväskylä and Aalto University in Finland. The study they conducted to test their development shows that nanostructures constructed of DNA molecules can be programmed to function as pH-responsive cargo carriers. This research paves the way towards functional drug-delivery vehicles.
To make the DNA nanostructure the team built a capsule-like carrier that can be loaded — or packed — with a variety of cargo, closed for delivery and opened again through a subtle pH increase. In other words, they built a nanocapsule that opens and closes according to the pH level of the surrounding solution.
Technically, it is a DNA origami structure, like a capsule, with pH-responsive DNA strands.
Such dynamic DNA nano-designs are usually controlled by hydrogen-bonding of two complementary DNA sequences. Here, one half of the capsule was equipped with specific double-stranded DNA domains. Then the double-stranded DNA domains could further form a DNA triple helix, a helical structure comprised of three, not just two DNA molecules – by attaching to a suitable single-stranded DNA in the other half.
Doctoral student Heini Ijäs from the Nanoscience Center at the University of Jyvaskyla and first author of the study explained:
The triplex formation can happen only when the surrounding pH of the solution is right. We call these pH-responsive strands “pH latches,” because when the strands interact, they function similarly to their macroscopic counterparts and lock the capsule in a closed state. We included multiple motifs into our capsule design to facilitate the capsule opening/closing based on cooperative behaviour of the latches. The opening of the capsule is actually very rapid and requires only a slight pH increase in the solution.
Nanoparticles and enzymes could be loaded and encapsulated within the capsules because the team designed the capsule with a cavity that could host different materials. This enabled for transporting molecular payloads or therapeutic substances, for example.
Through their study, the researchers demonstrated that both gold nanoparticles and enzymes (high pH) could be loaded and encapsulated within the capsules (low pH.) They saw that the cargo remained fully functional throughout the process by monitoring the enzyme activity.
Veikko Linko, Adjunct Professor at Aalto University, said:
The most intriguing thing about the DNA origami capsules is that the threshold pH at which the opening and closing take place is fully adjustable by selecting the base sequences of the pH latches. We designed the threshold pH to be 7.2-7.3, close to the blood pH. In the future, this type of drug carrier could be optimized to selectively open inside specific cancer cells, which can maintain a higher pH than normal healthy ones.
Even at physiological magnesium and sodium concentrations, and in 10% blood plasma, the capsules remained functional. They believe the capsules may continue to at even higher plasma concentrations. This research helps pave the way for developing smart and fully programmable drug-delivery vehicles for nanomedicine. The study was published in ACS Nano.
