New UF-developed DNA nanotrain steams through cancer cells

Chugging through cancerUF researchers have developed a “DNA nanotrain” that fast-tracks its payload of cancer-fighting drugs and bioimaging agents to tumor cells deep within the body. The nanotrain’s ability to cost-effectively deliver high doses of drugs to precisely target cancers and other medical maladies without leaving behind toxic nano-clutter has been the elusive Holy Grail for scientists studying the teeny-tiny world of DNA nanotechnology.

DNA nanotechnology holds great promise as a new way to deliver chemotherapy directly to cancer cells, but until now, scientists have not been able to direct nanotherapies to consistently differentiate cancer cells from healthy ones. Other limiting factors include high costs, too-small amounts of drugs delivered and potential toxic side effects.

“Most nanotechnology relies on a nanoparticle approach, and the particles are made of inorganic materials; after they’ve been used as a carrier for the drug, they’ll be left inside the body,” said the study’s lead investigator, Weihong Tan, Ph.D., a UF distinguished professor of chemistry, a professor of physiology and functional genomics, and a member of the UF Health Cancer Center and the UF Genetics Institute. “Compared to existing nanostructures, our nanotrain is easier and cheaper to make, is highly specific to cancer cells, has a lot of drug-loading power and is very much biocompatible.”

“The beauty of the nanotrain is that by using different disease biomarkers you can hitch different types of DNA probes as the train’s ‘locomotive’ to recognize and target different types of cancers.” — Weihong Tan, Ph.D.

Described in the Proceedings of the National Academy of Sciences, Tan’s DNA nanotrain is a three-dimensional structure composed of short strands of DNA tethered together into one long train. On the end of the nanotrain is an aptamer, a tiny piece of nucleic acid serving as the train’s “locomotive” on biochemical autopilot to home in on and bind to specific cancer cells. Trailing behind are tethered DNA structures that serve as side-by-side, high-capacity “box cars,” transporting bioimaging agents or drug cargos to their targets.

“We’ve precisely targeted leukemia, lung and liver cancer cells, and because the DNA probes are so precise in targeting only specific types of cancer cells we’ve seen dramatic reduction in drug toxicity in comparison to standard chemotherapies, which don’t discriminate well between cancerous and healthy cells,” Tan said. — Lindy Brounley

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