All aboard the nano train

All aboard the nanotrain

New UF-developed DNA nanotrain chugs through cancer cells

 By Lindy Brounley

UF 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 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.”

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.

“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,” Tan said. “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 and his colleagues say the DNA nanotrains can be cost-effectively made by mixing bits of DNA in a liquid medium. The mixture is then exposed to a compound that stimulates the pieces of DNA to seek each other out and self-assemble into the DNA nanotrains. The type of cancer cell the DNA nanotrain will seek out and destroy is determined by the specific compound added to the mixture as the trigger.

The study demonstrated in human cells and in mice that the DNA nanotrains exclusively target the cancer cells for which their probes were programmed. The DNA probes go straight to the cancer cells, leading the nanotrains to dock on the cell membranes and gain entry into the cells. Once inside, the drug payloads disperse, killing the cancer cells. The biodegradable components of the DNA nanotrains decay with the dead cancer cells and are removed by the body’s normal housekeeping mechanisms.

“It’s very exciting,” Tan said. “But we still have a long way to go before human trials.”