DNA origami guides new possibilities in the fight against pancreatic cancer

CHAMPAIGN, Ill. — 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. A new study uses DNA origami structures to selectively deliver fluorescent imaging agents to pancreatic cancer cells without affecting normal cells.

The study, led by University of Illinois Urbana-Champaign mechanical science and engineering professor Bumsoo Han and professor Jong Hyun Choi at Purdue University, found that specially engineered DNA origami structures carrying imaging dye packets can specifically target human KRAS mutant cancer cells, which are present in 95% of pancreatic cancer cases.

“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 Han, who is also affiliated with the Cancer Center at Illinois. “The current process of cancerous tissue removal through surgical resection can be improved greatly by more accurate imaging of tumor margins.”

The findings of the study are published in the journal Advanced Science.

DNA is a long double-stranded molecule, making it an ideal candidate for folding into nanoscale scaffolds that hold molecules — in this case, fluorescent imaging dyes — in place and to create new, synthetic molecular structures.

The team developed pancreatic cancer models using 3D printed “tumoroids” and microfluidic systems that mimic the complex tumor microenvironment — called microfluidic tumor-stroma models — to reduce the reliance on animal tissue and accelerate translation to clinical use in humans. To test the uptake of the origami structures in cancerous tissues, the researchers added the dye-packed DNA structures to the tumor models and tracked their movement with fluorescence imaging. They then administered the dye-delivering structures to mice with human pancreatic tumor tissue to explore the distribution of the DNA origami packets in more physiologically relevant conditions.

The team experimented with different sizes of tube and tile-shaped DNA origami molecules. They found that tube-shaped structures about 70 nanometers in length and 30 nanometers in diameter, as well as ones that are about 6 nanometers in length and 30 nanometers in diameter, experienced the greatest uptake by the pancreatic cancer tissue while not being absorbed by the surrounding noncancerous tissue. Larger tube-shaped molecules and all sizes of tile-shaped molecules did not perform as well.

“We were surprised to see how drastically the variation in size and shape of the DNA origami packets influenced uptake by cancer cells versus healthy cells,” Han said. “I thought that smaller would be better, so that there would be more accumulation, but it looks like there is a certain sweet spot for not just size but also shape.”

The next step is to explore the use of origami-folded DNA molecules loaded with chemotherapy drugs for selective delivery to cancer cells without affecting normal cells, Han said. “Doing so with engineered tumor models to reduce animal use and accelerate translation in drug discovery is another direction we are very proud of.”

This research was supported by grants from the National Institutes of Health and the National Science Foundation. Han also is affiliated with the bioengineering, the Carl R. Woese Institute for Genomic Biology, the Materials Research Laboratory and the Beckman Institute for Advanced Science and Technology.

Editor’s note:   

To reach Bumsoo Han, email bumsooh@illinois.edu.

The paper “DNA origami-cyanine nanocomplex for precision imaging of KRAS-mutant pancreatic cancer cells” is available online. DOI: 10.1002/advs.202410278

This work was supported by the National Institutes of Health grants U01 HL143403, R01 CA254110, U01 CA274304, UM1TR004402, P30 CA023168 and the National Science Foundation grant MCB-2134603.

Mechanical science and engineering is part of The Grainger College of Engineering at Illinois.