Non-infectious illnesses like cancer and cardiovascular diseases are rising globally, but they are hard to diagnose because of lack of biomarkers, and in countries with poor infrastructure, expensive diagnosis using mammograms and colonoscopy is not available to many.
Now, a team has developed a test that uses injected nanoparticles that find diseased tissue and produce a biomarker in urine that can be detected within minutes using paper strips rather like a home pregnancy test.
The researchers, from the Massachusetts Institute of Technology (MIT), Cambridge, report in the Proceedings of the National Academy of Sciences, PNAS, how they tested the new method in mice, using a single injection and a paper-strip urine analysis, to successfully detect diseases as diverse as solid cancer and blood clots.
They conclude that the experimental test offers the opportunity to develop a cheap diagnostic tool for a range of diseases – without the need for expensive invasive procedures or trained medical staff – that could be invaluable in countries with limited medical resources or infrastructures.
The technology is being developed by senior author Sangeeta Bhatia, MIT professor and Howard Hughes Medical Institute investigator, who explains:
“When we invented this new class of synthetic biomarker, we used a highly specialized instrument to do the analysis. For the developing world, we thought it would be exciting to adapt it instead to a paper test that could be performed on unprocessed samples in a rural setting, without the need for any specialized equipment. The simple readout could even be transmitted to a remote caregiver by a picture on a mobile phone.”
The technology uses nanoparticles that interact with tumor proteins, each of which produces hundreds of synthetic biomarkers that are easy to detect in urine.
The researchers started working on the idea in 2012 when faced with the problem that tumors are hard to detect via biomarkers because they produce very weak signals. One group of signals is in the form of proteins called matrix metalloproteinases (MMPs), which help cancer cells migrate from their original sites.
The researchers thought, if they could amplify these signals somehow, that might lead to a detectable biomarker.
As such, they developed nanoparticles coated with short protein fragments that attract different MMPs. The result is the nanoparticles concentrate at tumor sites, where the MMPs chop up the peptides (releasing hundreds of peptide fragments per MMP molecule), which then collect in the kidneys and pass out of the body in urine.
At first, the only way to detect the presence of the peptides in the urine was using a mass spectrometer that reads their molecular signal. But this is a very expensive piece of kit, so the researchers looked for other ways to analyze the urine and came up with a paper-based approach called “lateral flow assay,” which is used in pregnancy tests.
The paper strips are impregnated with antibodies that capture the peptides, which then flow along to invisible test lines further along the strip that become visible when they encounter particular peptides.
The researchers say the strips can be made to detect different stages or types of disease – it is a matter of coating the nanoparticles with different peptides and creating test lines that are uniquely sensitive to them.
Samuel Sia, an associate professor of biological engineering at Columbia University, New York, NY, who was not involved in the research, says the new technology is a “clever and inspired” way of detecting clinical conditions with unusually high protein levels in the body by testing compounds that exit the body.
“Extending this technology to detection by strip tests is a big leap forward in bringing its use to outpatient clinics and decentralized health settings,” he adds.
Having successfully demonstrated that the nanoparticle injections and paper strips can detect colon tumors and blood clots in mice, Prof. Bhatia says the next step is to test them in human patients.
Funds for the study came from various sources, including the National Institutes of Health, the Burroughs Wellcome Fund, the National Cancer Institute and the Howard Hughes Medical Institute.
Meanwhile, Medical News Today recently reported another study published in Nature Nanotechnology, where researchers at the University of Illinois at Chicago describe how they used nanoparticles to target inflammation-causing immune cells without interfering with correctly functioning immune cells.