APRIL 25, 2023, NEW YORK – Researchers led by Ludwig MIT’s Sangeeta Bhatia have designed a new type of nanoparticle sensor that could enable the early detection of cancer with a simple urine test. The sensors, which can detect many different proteins associated with cancer at once, could also be used to distinguish the type of a tumor, state of disease progression or how a cancer is responding to treatment. Their description and preclinical evaluation of the technology appears in the current issue of Nature Nanotechnology.
The nanoparticles employed in the test are designed to shed unique sequences of DNA—or DNA barcodes—when they encounter a tumor. Those DNA barcodes, which collect in the urine, can reveal distinguishing features of a particular patient’s tumor. The researchers designed their test so that it can be performed using a strip of paper, much like an at-home Covid test.
Over the past several years Bhatia—who is also the John and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science—and her colleagues have devised diagnostic tests that exploit protease expression in tumors to detect cancer. The tests identify proteases, protein-snipping enzymes whose expression varies by cancer type and disease state, by detecting their cleavage of target peptides on nanoparticles that make their way into tumors.
In the current study, Bhatia and her colleagues attached to the peptides DNA barcodes that are chemically modified to prevent their degradation in the body. When proteases in tumors cut the peptides, the DNA barcodes are released and eliminated from the body in urine, where they are identified using a programmable DNA-targeting system known as CRISPR linked to a DNA cutting enzyme called Cas12a. When a particular DNA barcode is present in the sample, Cas12a amplifies its signal so that it can be seen as a dark strip on the paper test—or, alternatively, a distinct fluorescent signal.
Bhatia and her colleagues showed that the nanoparticles employed in the test can be designed to carry many different DNA barcodes, each of which detects a different type of protease activity, enabling “multiplexed” sensing. Using a larger number of sensors boosts the sensitivity and specificity of the test, allowing researchers to more easily distinguish between tumor types.
The researchers showed that they could use the sensors to detect the activity of five different enzymes that are expressed in tumors, and could differentiate between primary and metastatic tumors in the lungs of mice.
They also showed that their approach could be scaled up to distinguish at least 46 different DNA barcodes in a single sample, using a microfluidic device to analyze the samples.
This summary is derived from an MIT News article that is available here.