New sensor for MRI and fluorescent imaging

Nanoparticles capable of simultaneously performing fluorescent and magnetic resonance imaging (MRI) in living animals have been developed by chemists at MIT. These particles could track specific molecules produced in the body, monitor tumour environment, or determine whether drugs have successfully reached their targets. They carry distinct sensors for fluorescence and MRI to track vitamin C in mice. If the concentration is high, the particles show a strong fluorescent signal but little MRI contrast. If there is little vitamin C, a stronger MRI signal is visible but fluorescence is weak. The particles can be assembled from polymer chains carrying either nitroxide - an organic MRI contrast agent - or a fluorescent molecule called Cy5.5. When mixed together in a desired ratio – in this case 99:1 - they join to form specific nanosized structures called branched bottlebrush polymers. Nitroxides - reactive molecules containing a nitrogen atom bound to an oxygen atom with an unpaired electron - suppress Cy5.5’s fluorescence, but when they encounter molecules such as vitamin C from which they can grab electrons, they become inactive and Cy5.5 fluoresces. Typically nitroxides have a very short half-life in living systems, but this can be extended by attaching two bulky structures to them. Incorporating these into the branched bottlebrush polymers leads to improvements in the nitroxide lifetime meaning they can circulate in a mouse’s bloodstream for long enough to obtain useful MRI images. The particles accumulated in the liver where they grabbed electrons from vitamin C, turning off the MRI signal and boosting fluorescence. Researchers found no MRI signal but some fluorescence in the brain - a destination for much of the vitamin C produced in the liver, and maximal MRI contrast in the blood and kidneys, where vitamin C concentration is low. The researchers hope to enhance the signal differences obtained when the sensor encounters a target molecule. They have also created nanoparticles carrying the fluorescent agent plus up to three different drugs to enable them to track whether the nanoparticles are delivered to their targeted locations. “That’s the advantage of our platform — we can mix and match and add almost anything we want,” said Jeremiah Johnson, assistant professor of chemistry and senior author of the Nature Communications study. The particles could be used to evaluate the level of oxygen radicals in a patient’s tumour, revealing valuable information about how aggressive the tumour is. “We think we may be able to reveal information about the tumour environment with these kinds of probes, if we can get them there,” Johnson said. “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.”