「 Technology Feature--Small RNAs: The Inside Track 」
How to deliver short-interfering RNAs (siRNAs) to specific tissues is only part of the problem facing researchers. They also need to find out whether the RNA has reached its intended target. Anna Moore, a radiologist at Harvard Medical School in Boston, Massachusetts, is well aware of the issue. "There was no way to use a clinical imaging modality to see the delivery of siRNA," she says.
When researchers want to see whether an siRNA has been reached a particular tissue, they usually perform histological analysis followed by reverse transcription PCR to see whether the target gene was silenced. "You can do this with mice, but when you move on to humans it becomes impractical," Moore says.
NATURE MED. (REF. 1)
Now you see it: the nanoparticle system devised by Anna Moore's team allows siRNA delivery to be seen in MRI scans (top) and optical scans (bottom).
Researchers can track siRNAs in vivo using bioluminescence imaging or by tracking green fluorescent proteins. But bioluminescence imaging is not a clinical modality. So Moore and her colleagues decided to try magnetic resonance imaging (MRI).
The first step was to design an siRNA delivery vehicle that could be imaged by MRI. Moore and her team used a nanoparticle containing an iron oxide core. They coated it with dextran, which could have various targeting features added to it relatively easily. Although iron oxide can be imaged using MRI, the group also attached a fluorescent dye, Cy 5.5, to the dextran coat for optical imaging. "We wanted to correlate the imaging data with microscopic findings," says Moore.
The iron oxide nanoparticle generates a bright spot on the MRI image. The exact target of the nanoparticle can then be confirmed by the fluorescent dye and by doing microscopy for histological analysis.
Two further attachments were then made to the nanoparticle via the dextran coating: a membrane translocation peptide that can cross cell membranes and an siRNA. With this, Moore and her colleagues thought they had a particle that could target and image delivery to tumour cells in vivo. But the imaging showed that the nanoparticle went to the liver and kidneys, and was present in other organs as well1.
Moore and her team plan to continue with the nanoparticles, trying to make them more efficient in terms of delivery and target uptake. But the real value of these nanoparticles might be their versatility. As different siRNAs or targeting peptides can be attached to the dextran coat, a large range of therapeutic siRNAs and peptides can be tested.
"My lab is really interested in imaging other pathologies such as diabetes, which is far from cancer but the imaging approaches are very similar," says Moore. "And that is the beauty of this technology — you can apply it to different pathologies."
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