QUANTUM dots – tiny pieces of semiconductor – have already proven their worth in medical imaging thanks to their bright rainbow colours. Now it turns out they’re also extremely good at making deliveries inside living cells.
This is great news for the technology of RNA interference (RNAi), which involves blocking the action of messenger RNA, the molecule that carries the chemical “blueprint” of proteins from the genes in a cell’s nucleus to the ribosomes where the proteins are made. If the messenger RNA is intercepted, the protein is no longer produced and the gene is said to have been “silenced”. That’s helpful when trying to work out what individual genes do. It’s also a potentially valuable treatment for a wide variety of diseases caused by genetic faults, including many types of cancer.
RNAi can be induced by introducing “small interfering RNA” (siRNA) – short sections of an RNA strand complementary to the messenger RNA. The siRNA binds with the messenger RNA and cleaves it into useless pieces by exploiting the normal workings of the cell.
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That’s the theory, but in practice it can be difficult to get the siRNA into living cells. Not only does the siRNA have to pass through the cell membrane – usually done by incorporating it into fatty spheres, or attaching it to charged polymers – but once inside it also has to pass unscathed through the cell’s internal machinery. This includes sacs known as endosomes, which transport material around the cell and tend to swallow the siRNA up or deliver it to lysosomes, where it is digested by enyzmes. These problems have meant that success rates have been low.
Xiaohu Gao of the University of Washington in Seattle and colleagues were using quantum dots to image the outside of cells when they noticed that the dots passed naturally through the cell membrane. So they coated the dots with positively-charged chemical groups, to which the negatively-charged siRNAs were attracted, allowing the dots to carry them easily into the cell.
Even better, the dots – whose movements could be tracked thanks to their fluorescence – were escaping the clutches of the endosomes: the positive charge raised the osmotic pressure inside the sacs until they burst.
The quantum-dot technique turned out to be much more effective at silencing genes than other approaches. For example, the cell’s production of a test protein dropped to just 2 per cent compared with a fall to 13 per cent when the siRNA was introduced using fatty spheres.
“This is an exciting piece of work,” says Weihong Tan, associate director of the University of Florida’s Center for Research at the Bio/Nano Interface. “This method is simpler, more efficient and less toxic than previous work using siRNA conjugates.”
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