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July 7, 2008
Quantum dots deliver gene silencers better

FROM STAFF REPORTS

Emory and University of Washington scientists recently reported one of the first applications of nanotechnology known as quantum dots to drug delivery.

They described a method for introducing gene-silencing tools made of RNA into cells that is 10 to 20 times more effective than existing methods.

Smuggling genetic material in the form of RNA into cells potentially could be used to treat conditions ranging from breast cancer to deteriorating eyesight.

The discovery that short pieces of RNA can silence a stretch of genetic code, a process known as RNA interference, earned a Nobel Prize in 2006, but applying it in living cells has been difficult.

“This work helps to overcome the longstanding barrier in the field: how to achieve high silencing efficiency with low toxicity,” co-author and Emory/Georgia Tech bioengineer Shuming Nie says.

Emory postdoctoral fellow Maksym Yezhelyev, breast cancer expert Ruth O’Regan and Nie collaborated with postdoctoral fellow Lifeng Qi and assistant professor Xiaohu Gao at the University of Washington. Their results were published online in the June 21 issue of the Journal of the American Chemical Society.
The team’s method marries quantum dots, which Nie has already made famous for their light-emitting properties, with chemical sensors called “proton sponges.”

The proton sponges cloak the RNA so that it can pass through the cell membrane and then release it upon reaching the endosome, a fatty bubble that surrounds incoming material. The RNA then accumulates in the cell, where it can do its gene-silencing work.

Key to the new approach is that researchers can adjust the chemical makeup of the quantum dot’s proton-sponge coating, allowing the scientists to precisely control how tightly the dots attach to the RNA.

Also, fluorescent quantum dots allow scientists to watch the interfering RNA’s movements. Previous trackers gave off light for less than a minute, while quantum dots, developed for imaging, emit light for hours at a time. In the experiments the authors were able to watch the process for many hours to track the gene-silencer’s path.

“Looking forward, this work will have important implications in in-vivo therapeutics, which will require the use of nontoxic iron oxide and biodegradable polymeric carriers rather than quantum dots,” Nie says.

Quantum dots are not yet approved for use in humans. The authors are now transferring their techniques to particles of iron oxide, which have been approved by the U.S. Food and Drug Administration. They are also working to target cancer cells by attaching to specific markers on the cells’ surface.