Scientists at MIT say they have
developed a simple, cheap paper test that could be used to improve cancer diagnosis
rates and help people get treated earlier. The diagnostic, which works much
like a pregnancy test, reportedly could reveal within minutes, based on a urine
sample, whether a person has cancer. This approach has helped detect infectious
diseases, and the new technology allows noncommunicable diseases to be detected
using the same strategy.
The technique, developed by MIT
professor and Howard Hughes Medical Institute investigator Sangeeta Bhatia,
Ph.D., relies on nanoparticles that interact with tumor proteases, each of
which can trigger release of hundreds of biomarkers that are then detectable in
a patient's urine.
“When we invented this new class of
synthetic biomarker, we used a highly specialized instrument to do the
analysis,” said Dr. Bhatia. “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.”
Dr. Bhatia, who is also a member of
MIT's Koch Institute for Integrative Cancer Research and Institute for Medical
Engineering and Science, is the senior author of a paper (“Point-of-care
diagnostics for noncommunicable diseases using synthetic urinary biomarkers and
paper microfluidics”) describing the particles in Proceedings of the National
Academy of Sciences.
In 2012, Dr. Bhatia and colleagues
introduced the concept of a synthetic biomarker technology to amplify signals
from tumor proteins that would be hard to detect on their own. These proteins,
known as matrix metalloproteinases (MMPs), help cancer cells escape their
original locations by cutting through proteins of the extracellular matrix,
which normally holds cells in place.
The MIT nanoparticles are coated
with peptides targeted by different MMPs. These particles congregate at tumor
sites, where MMPs cleave hundreds of peptides, which accumulate in the kidneys
and are excreted in the urine.
In the original version of the
technology, these peptides were detected using a mass spectrometer. However,
these instruments are not readily available in the developing world, so the
researchers adapted the particles so they could be analyzed on paper, using a
lateral flow assay.
“We describe
the design of exogenous agents that serve as synthetic biomarkers for NCDs
[noncommunicable diseases] by producing urinary signals that can be quantified
by a companion paper test. These synthetic biomarkers are composed of
nanoparticles conjugated to ligand-encoded reporters via protease-sensitive
peptide substrates,” wrote the investigators. “Upon delivery, the nanoparticles
passively target diseased sites…where up-regulated proteases cleave the peptide
substrates and release reporters that are cleared into urine. The reporters are
engineered for detection by sandwich immunoassays, and we demonstrate their
quantification directly from unmodified urine.”
In tests in
mice, the researchers were able to accurately identify colon tumors as well as
blood clots. Dr. Bhatia says these tests represent the first step toward a
diagnostic device that could someday be useful in human patients.
- Tomado de genengnews.com