Investigators at the University of Florida have developed what they are calling a “DNA nanotrain” that fast-tracks its payload of cancer-fighting drugs and bioimaging agents to tumor cells deep within the body. These nanotrains have the potential to cost-effectively deliver high doses of drugs to precisely targeted cancers using biocompatible materials that fall apart into non-toxic components once their payload is delivered.
Developed by Weihong Tan and his colleagues, the nanotrains are highly specific to cancer cells and can carry large payloads of one or more compatible drugs. The Florida research team published its work in the Proceedings of the National Academy of Sciences.
“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,” Dr. 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.”
Dr. Tan and his colleagues report that the DNA nanotrains can be cost-effectively made by mixing short fragments of DNA in a liquid medium. These fragments, while inexpensive to synthesize, create unique structures that give the nanotrains their potential: an “engine” fragment with DNA-structured aptamers which (like an antibody) can target specific structural features of cancer cells and “boxcar” fragments with gaps where drugs can be loaded to high capacities. These fragments are then mixed and exposed to a compound that stimulates the pieces of DNA to seek each other out and self-assemble into the DNA nanotrains.
Their studies have demonstrated in vitro 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, a process Dr.Tan and his team were able to monitor in real time by measuring the amount of fluorescent light emitted when the drug is released. The biodegradable components of the DNA nanotrains decay with the dead cancer cells and are removed by the body’s normal housekeeping mechanisms.
The investigators report that when loaded with anticancer drugs, these nanotrains inhibited tumor growth and improved survival in mice more than in those that received drugs injected freely into the bloodstream. Additionally, the mice that were treated with nanotrain drug delivery experienced reduced toxicity as shown by less weight loss and better physical condition than the mice that received injected drug therapy. Dr. Tan and his colleagues are now working to identify optimum dosage using mouse models for T-cell leukemia, lung cancer, liver cancer, and triple negative breast cancer.
This work, which was supported in part by the National Cancer Institute, is detailed in a paper titled, “Self-assembled, aptamer-tethered DNA nanotrains for targeted transport of molecular drugs in cancer theranostics.” An abstract of this paper is available at the journal’s website.
News Release; National Cancer Institute; July, 2013