Nav: Home

A cautionary tale for researchers working on selective drug delivery

May 09, 2019

Many studies indicating that DNA nanostructures can enter cells more readily than simple DNA strands are flawed, according to researchers at McGill University. In a paper published in the American Chemical Society journal ACS Central Science, the McGill scientists demonstrate that many DNA cage nanostructures aren't taken up by cells to a significant extent. In a series of experiments, they show, instead, that the DNA nanostructures are degraded by enzymes outside the cell; a fluorescent dye used for tracking purposes separates from the nanostructure; and the dye - or a small fragment containing the dye - is taken up in cells. The resulting fluorescent signal from within the cell is easily misinterpreted as indicating that the nanostructure, itself, has entered the cell. The group also shows that a commonly used fluorescence experiment (called FRET), involving energy transfer between two dyes on a structure can also give erroneous results.

This finding is significant, because DNA strands are considered a promising tool for stopping the production of proteins associated with disease - yet delivering the strands into cells is a technical challenge. "Our paper is a cautionary tale for scientists working in the field of DNA/RNA delivery through selective therapeutics," says senior author Hanadi Sleiman, Professor of Chemistry at McGill and Canada Research Chair in DNA Nanoscience.

This problem could, however, be turned into an advantage, notes lead author Aurélie Lacroix, a graduate student in Prof. Sleiman's lab. "We could attach molecules on DNA nanostructures that make them enter diseased cells - for example cancer cells - but not normal cells. This would make it possible to selectively deliver drugs into diseased cells." Sleiman also insists that some DNA nanostructures have shown exceptional promise in animal studies.

The McGill team offers recommendations and guidelines for scientists performing cell uptake studies using fluorescent dyes, to ensure that research is reliable and reproducible.
-end-
Funding for this study was provided in part by the Natural Sciences and Engineering Research Council of Canada, the Canadian Institutes of Health Research, the Canada Foundation for Innovation, the Canada Research Chairs Program, and the Fonds de recherche du Québec - Nature et technologies.

"Uptake and Fate of Fluorescently Labeled DNA Nanostructures in Cellular Environments: A Cautionary Tale", Aurélie Lacroix, et al, ACS Central Science, published online April 26, 2019. https://pubs.acs.org/doi/10.1021/acscentsci.9b00174

McGill University

Related Research Articles:

More Research News and Research Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Clint Smith
The killing of George Floyd by a police officer has sparked massive protests nationwide. This hour, writer and scholar Clint Smith reflects on this moment, through conversation, letters, and poetry.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.