Nanoparticles that enable both MRI and fluorescent imaging could monitor cancer, other diseases.
MIT chemists have developed new nanoparticles that can simultaneously perform magnetic resonance imaging (MRI) and fluorescent imaging in living animals. Such particles 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 paper appearing in the Nov. 18 issue of Nature Communications, the researchers demonstrate the use of the particles, which carry distinct sensors for fluorescence and MRI, to track vitamin C in mice. Wherever there is a high concentration of vitamin C, the particles show a strong fluorescent signal but little MRI contrast. If there is not much vitamin C, a stronger MRI signal is visible but fluorescence is very weak.
Future versions of the particles 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.
“You may be able to learn more about how diseases progress if you have imaging probes that can sense specific biomolecules,” Johnson says.
Johnson and his colleagues designed the particles 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.
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 of the new Nature Communications paper, recently discovered that their half-life can be extended by attaching two bulky structures to them. Furthermore, the authors of the Nature Communications paper show 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 can 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.
Mixing and matching
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.
“That’s the advantage of our platform — we can mix and match and add almost anything we want,” Johnson says.
These particles 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.”
Steven Bottle, a professor of nanotechnology and molecular science at Queensland University of Technology, says the most impressive element of the study is the combination of two powerful imaging techniques into one nanomaterial.
“I believe this should deliver a very powerful, metabolically linked, multi-combination imaging modality which should provide a highly useful diagnostic tool with real potential to follow disease progression in vivo,” says Bottle, who was not involved in the study.
The research was funded by the National Institutes of Health, the Department of Defense, the National Science Foundation, and the Koch Institute for Integrative Cancer Research.
Sarah McDonnell | EurekAlert!
New way to look at cell membranes could change the way we study disease
19.11.2018 | University of Oxford
Controlling organ growth with light
19.11.2018 | European Molecular Biology Laboratory
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
19.11.2018 | Event News
09.11.2018 | Event News
06.11.2018 | Event News
19.11.2018 | Materials Sciences
19.11.2018 | Information Technology
19.11.2018 | Life Sciences