Chemists at the Massachusetts Institute of Technology (MIT; Cambridge, MA) have developed new nanoparticles that can perform fluorescence imaging along with magnetic resonance imaging (MRI) in living animals. Such nanoparticles could help scientists to track specific molecules produced in the body, monitor a tumor's environment, or determine whether drugs have successfully reached their targets.
In a study, the researchers demonstrated the use of the nanoparticles, which carry distinct sensors for fluorescence imaging and MRI, to track vitamin C in mice. Wherever there was a high concentration of vitamin C, the nanoparticles showed a strong fluorescent signal but little MRI contrast. If there was not much vitamin C, a stronger MRI signal was visible but fluorescence was very weak.
Future versions of the nanoparticles could be designed to detect reactive oxygen species that often correlate with disease, says Jeremiah Johnson, an assistant professor of chemistry at MIT and senior author of the study. They could also be tailored to detect more than one molecule at a time. And with imaging probes that sense specific biomolecules, Johnson says, researchers could learn more about how diseases progress.
Johnson and his colleagues designed the nanoparticles so they can be assembled from building blocks made of polymer chains carrying either an organic MRI contrast agent called a nitroxide or a fluorescent molecule called Cy5.5.
When mixed together in a desired ratio, these building blocks join to form a specific nanosized structure the authors call a branched bottlebrush polymer. For this study, they created particles in which 99 percent of the chains carry nitroxides, and 1 percent carry Cy5.5.
|Illustration: Christine Daniloff/MIT|
Nitroxides are reactive molecules that contain a nitrogen atom bound to an oxygen atom with an unpaired electron. Nitroxides suppress Cy5.5’s fluorescence, but when the nitroxides encounter a molecule such as vitamin C from which they can grab electrons, they become inactive and Cy5.5 fluoresces.
Nitroxides typically have a very short half-life in living systems, but University of Nebraska chemistry professor Andrzej Rajca, who is also an author on the study, recently discovered that their half-life can be extended by attaching two bulky structures to them. Furthermore, the authors of the study showed that incorporation of Rajca’s nitroxide in Johnson’s branched bottlebrush polymer architectures leads to even greater improvements in the nitroxide lifetime. With these modifications, nitroxides could circulate for several hours in a mouse’s bloodstream—long enough to obtain useful MRI images.
The researchers found that their imaging particles accumulated in the liver, as nanoparticles usually do. The mouse liver produces vitamin C, so once the particles reached the liver, they grabbed electrons from vitamin C, turning off the MRI signal and boosting fluorescence. They also found no MRI signal but a small amount of fluorescence in the brain, which is a destination for much of the vitamin C produced in the liver. In contrast, in the blood and kidneys, where the concentration of vitamin C is low, the MRI contrast was maximal.
The researchers are now working to enhance the signal differences that they get when the sensor encounters a target molecule such as vitamin C. They have also created nanoparticles carrying the fluorescent agent plus up to three different drugs. This allows them to track whether the nanoparticles are delivered to their targeted locations.
These nanoparticles could also be used to evaluate the level of oxygen radicals in a patient’s tumor, which can reveal valuable information about how aggressive the tumor is.
“We think we may be able to reveal information about the tumor environment with these kinds of probes, if we can get them there,” Johnson says. “Someday you might be able to inject this in a patient and obtain real-time biochemical information about disease sites and also healthy tissues, which is not always straightforward.”
Full details of the study appear in the journal Nature Communications; for more information, please visit http://dx.doi.org/10.1038/ncomms6460.
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