Doctors and researchers need to see into bodies to accurately diagnose and cure diseases. The basic x-ray has come a long way in medical imaging, but most current instruments are still too coarse to measure quantities or specific types of cells inside the body’s deep tissues.
According to new studies conducted in mice by the University of Illinois, quantum dots can accomplish this.
“Quantum dots can measure things in the body that are very, very dynamic and complicated and that we can’t see currently. They give us the ability to count cells, detect their exact locations, and observe changes over time. I think it is really a huge advance,” says Andrew Smith, professor in the Department of Bioengineering at U of I and co-author on the ACS Nano study.
Quantum dots are nanoparticles that are created in a lab and have unique optical properties that can be detected using standard microscopy, tomography (e.g., PET/CT scanners), and fluorescence imaging. Bioengineers like Smith can make them glow in certain colors and produce light in the infrared range depending on their size and composition.
“Emitting light in the infrared is rare. Very little light is emitted by tissues in the infrared, so if you put them in the body, they appear very bright. We can see deeply into the body and can more accurately measure things than we could using technology in the visible range,” Smith says.
In the ACS Nano study, Smith and colleagues let quantum dots loose on macrophages.
Macrophages are activated when our systems need to eat infections or clear up cellular trash. One of its responsibilities is to cause inflammation, which makes the environment hostile to dangerous microorganisms.
Quantum dots put out a huge amount of light, giving us the ability to measure specific cell types to a greater degree and identify where they are. That degree of light output allows the use of optical techniques, which are much more accessible than other imaging technologies. Compared with MRI and PET scanners, they’re cheap instruments that can be put into a small clinic. Everybody could have one.Andrew Smith
However, they might occasionally be too good at what they do. Chronic inflammation caused by macrophage activity can lead to diabetes, cardiovascular problems, malignancies, and more, depending on the tissue they’re in. The macrophages in fat, or adipose tissue, were of particular interest to the University of Illinois scientists.
“With weight gain and obesity, macrophage numbers are known to increase in adipose tissue and tend to shift towards an inflammatory phenotype, which contributes to the development of insulin resistance and metabolic syndrome. The number and location of macrophages in adipose tissue are poorly described, especially in vivo,” says Kelly Swanson, Kraft Heinz Endowed by the Company Professor of Human Nutrition at the Department of Animal Sciences at the University of Iowa and co-author of the paper.
“The quantum dots our group developed allow for better quantification and characterization of the cells present in adipose tissue and their spatial distribution,” he adds.
Quantum dots coated with dextran, a sugar molecule that similarly targets macrophages in fat tissue, were developed by the researchers. They injected these quantum dots into obese mice as a proof-of-concept and compared imaging findings to dextran alone, the current standard for imaging macrophages.
Across all imaging platforms, including simple optical approaches, quantum dots beat dextran alone.
“Quantum dots put out a huge amount of light, giving us the ability to measure specific cell types to a greater degree and identify where they are,” Smith says. “That degree of light output allows the use of optical techniques, which are much more accessible than other imaging technologies. Compared with MRI and PET scanners, they’re cheap instruments that can be put into a small clinic. Everybody could have one.”
Despite the fact that quantum dots have yet to be employed in people, Swanson envisions a future in which a simple optical technique such as ultrasonography may be used to non-invasively diagnose and track inflammatory macrophages in obese individuals.
“There could be a device like an ultrasound where you scan somebody, and even if a patient’s weight hasn’t changed, a doctor could tell if the cell types are changing. More inflammatory cells could predict insulin resistance and other issues,” he says. “That’s why I’m interested in it, for its diagnostic properties.”
Quantum dots aren’t utilized in people since they’re often created with heavy metals like cadmium and mercury, and scientists aren’t sure how they’re digested and eliminated.
Quantum dots built with safer elements are being developed by Smith and his colleagues, but they are still a vital research tool in the meanwhile. For example, their nine-times-longer circulation period than dextran in the current investigation could provide diagnosticians with a technique to move beyond a snapshot in time.
“There’s a huge level of variability of macrophages even across a day. Adipose tissue may have a very high number in the middle of the day, and then it drops way down,” Smith says.
“In animal studies, we can sacrifice animals at the start and end of a day to study the trend, but with quantum dots, we might not have to do that. You could track one animal over time to see its progression. Quantum dots offer a huge amount of value in animal studies. So even if quantum dots don’t make it to humans, if we never find a way to make them non-toxic, the value is still really great.”
A National Institutes of Health funding was recently awarded to Smith, Swanson, and other researchers to broaden their work with quantum dots to target dozens of different cell types. The University of Illinois Urbana-Animal Champaign’s Sciences Department is part of the College of Agricultural, Consumer, and Environmental Sciences.