Illinois bioengineers led by professor Xing Wang have developed a new, ionic liquid–based strategy for assembling DNA nanostructures that dramatically improves their stability and performance in biological environments. By replacing traditional magnesium ions with choline dihydrogen phosphate, the team created nanostructures that last longer and bind more precisely to protein biomarkers, including those on cancer cells, advancing their potential for targeted drug delivery. This breakthrough simplifies and lowers the cost of producing functional DNA nanostructures while enhancing their real-world biomedical viability. The work highlights a significant step forward in bioengineering-driven nanomedicine and cancer therapy design.
Written by Ben Libman
“We have developed a simpler, faster, and alternative assembly strategy for building DNA nanostructures that not only survive in harsh biological environments but also perform better. It’s like giving DNA nanostructures a protective suit for real-world biomedical applications.” -Professor Xing Wang, Department of Bioengineering
Professor Xing Wang
DNA nanostructures are exciting new biomedical tools with myriad potential in treatment, diagnosis and disease prevention. Made of folded DNA, these nanostructures are highly programmable and have been used in bioengineering professor Xing Wang’s lab before for virus rapid detection tests, potent inhibition and targeted cancer drug delivery.
Despite their promise, these structures degrade quickly in biological environments, limiting their potential. The culprits are magnesium ions. Though necessary for their assembly, magnesium ions also render DNA nanostructures unstable within most organisms, causing them to quickly degrade.
That is, until Wang and bioengineering graduate student Dhanush Gandavadi had a breakthrough, which was recently published in the Journal of the American Chemical Society. As an alternative to metal ions, the team began looking at ionic liquids such as choline dihydrogen phosphate (CDHP), which are liquid salts.
“Ionic liquids have traditionally been used in petrochemical, electrochemical, and battery applications,” Wang explained. “Since one of our research interests is focused on DNA nanostructure-enabled drug delivery and therapeutics, we wondered if we could assemble DNA nanostructures in ionic liquids and utilize their properties for potential therapeutic applications.”
A diagram from the lab's published paper in JACS.
The results exceeded the researchers’ expectations. Though Wang’s lab only set out to verify the nanostructures would retain functionality when assembled in this new way, the data indicated the structures’ ability to bind to protein biomarkers on a cell’s surface had improved, allowing for more precise targeting. The nanostructures even showed particular affinity when binding to cancer cells, something that had been difficult in previous magnesium-based assembly systems. The nanostructures produced by this new method also lasted far longer in simulated biological environments, in some cases up to 48 hours.
These findings have implications beyond DNA nanostructures, and may open the doors for new applications of ionic liquids in drug deliveries. “Our work suggests that ionic liquids could serve not only as coating but also as functional carriers for DNA nanostructures in drug delivery and therapy,” Wang said. “This dual role, protecting and enhancing binding, opens new avenues for designing nanomedicines.”
Wang’s lab is working to bring this new process into practical applications, saying “We’re now translating this platform toward cancer therapy and understanding how these ionic liquid-based DNA nanostructures perform in targeting and delivery payloads to cancer cells.”
In the future, Wang hopes that this new methodology of assembling DNA nanostructures will make this technology accessible to more labs. “Current assembly and stabilization strategies often involve multiple steps, high cost, and reduced functionality under physiological conditions,” he said. “Our method provides a one-stop, cost-effective alternative that yields stable and functional nanostructures, potentially useful for labs worldwide.”
Wang credits his collaborators, including professor Arun Richard at the University at Albany, who demonstrated the assembly of smaller tile-based DNA motifs in ionic liquids.
DNA nanostructures are an exciting forefront of biomedical technology, and Wang hopes to continue improving this field. With upgrades in the stability and performance of these tools, pioneered at Illinois, soon their full potential may be unlocked.
Xing Wang is a professor in the Department of Bioengineering, with appointments in the Department of Chemistry, Holonyak Micro & Nanotechnology Laboratory (MNTL), Carl R. Woese Institute for Genomic Biology (IGB), Center for Genomic Diagnostics (CGD), and Cancer Center at Illinois (CCIL).
Dhanush Gandavadi is a doctoral candidate in the Department of Bioengineering.