DNA Origami Improves Imaging of Dense Pancreatic Tissue for Cancer Detection and Treatment

One of the challenges of fighting pancreatic cancer is finding ways to penetrate the organ’s dense tissue to define the margins between malignant and normal tissue. Now, a new study uses DNA origami structures to selectively deliver fluorescent imaging agents to pancreatic cancer cells without affecting normal cells.

The research, conducted by scientists at the University of Illinois Urbana-Champaign (Champaign, IL, USA) and Purdue University (West Lafayette, IN, USA), revealed that DNA origami structures, which are engineered to carry packets of imaging dye, can selectively target human KRAS mutant cancer cells. These cells are present in approximately 95% of pancreatic cancer cases. DNA, being a long double-stranded molecule, is particularly suited for folding into nanoscale scaffolds capable of holding molecules—in this case, fluorescent dyes—at precise locations to form new, synthetic molecular structures.

Image: Professor Bumsoo Han and postdoctoral researcher Sae Rome Choi of Illinois co-authored a study on using DNA origami to enhance imaging of dense pancreatic tissue (Photo courtesy of Fred Zwicky/University of Illinois Urbana-Champaign)

In their experiments, the researchers created 3D models of pancreatic cancer using "tumoroids" and microfluidic systems that replicate the complex tumor microenvironment. These microfluidic tumor-stroma models were designed to reduce reliance on animal tissue and enhance the potential for translating these findings to human clinical applications. To test how effectively the DNA origami structures were taken up by cancerous tissues, the researchers applied the dye-packed DNA structures to the tumor models and monitored their movement using fluorescence imaging. They further tested the distribution of these DNA origami packets in a more biologically relevant environment by administering them to mice implanted with human pancreatic tumor tissue.

The team experimented with various DNA origami shapes, including tube-shaped and tile-shaped molecules. The results, published in the journal Advanced Science, showed that tube-shaped molecules measuring approximately 70 nanometers in length and 30 nanometers in diameter, as well as smaller versions about 6 nanometers in length and 30 nanometers in diameter, exhibited the highest uptake by pancreatic cancer tissue, without being absorbed by surrounding non-cancerous tissue. In contrast, larger tube-shaped molecules and all tile-shaped molecules showed less effective results. Looking ahead, the researchers plan to explore the use of DNA origami structures loaded with chemotherapy drugs for targeted delivery to cancer cells, further minimizing impact on normal cells.

“This research highlights not only the potential for more accurate cancer imaging, but also selective chemotherapy delivery, a significant advancement over current pancreatic ductal adenocarcinoma treatments,” said Bumsoo Han, a mechanical science and engineering professor at University of Illinois Urbana-Champaign. “The current process of cancerous tissue removal through surgical resection can be improved greatly by more accurate imaging of tumor margins.”