New diagnostics based on analysis of urine samples can also be designed to reveal whether a tumor has metastasized.
Engineers at MIT have designed a new nanoparticle sensor that allows early diagnosis of cancer with a simple urine test. Sensors that can detect many different oncoproteins can also be used to distinguish between tumor types and response to therapy.
The nanoparticles are designed to release short DNA sequences that are excreted in the urine when they encounter a tumor. Analysis of these DNA “barcodes” can reveal distinguishing features of a particular patient’s tumor. Researchers have designed the test so that it can be performed with a piece of paper, similar to the Covid test at home. We hope this will make it affordable and accessible to as many patients as possible.
“We are trying to innovate in the context of making technology accessible to low-resource and moderate-resource settings. It’s part of our goal to create an inexpensive technology that can provide an affordable answer,” said Sangeeta Bhatia, a professor of health sciences and technology and electrical engineering at John and Dorothy Wilson. She holds degrees in Computer Science and Computer Science from the Massachusetts Institute of Technology (MIT), and she is also a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Biomedical Engineering and Science.
In tests on mice, the researchers showed that the sensor could be used to detect the activity of five different enzymes expressed in tumors. They also used a microfluidic device to analyze the samples and showed that their approach could be scaled up to distinguish at least 46 different DNA barcodes in a single sample.
Bhatia is a senior author on the paper, published today in Nature Nanotechnology. Liangliang Hao, a former Massachusetts Institute of Technology (MIT) research scientist and now an assistant professor of biomedical engineering at Boston University, is the study’s lead author.
DNA barcode
For several years, Bhatia’s lab has been developing “synthetic biomarkers” that can be used to diagnose cancer. The study is based on the concept of detecting cancer biomarkers such as proteins and circulating tumor cells in patient blood samples. These naturally occurring biomarkers are so rare that they are almost impossible to spot, especially in early stages, but synthetic biomarkers can amplify the small changes that occur within small tumors. can.
In previous work, Bhatia created nanoparticles that could detect the activity of enzymes called proteases. Proteases help cancer cells escape from their original location or settle in a new location by cleaving proteins in the extracellular matrix. The nanoparticles are coated with peptides that are cleaved by various proteases, and once these peptides are released into the bloodstream they become concentrated and more easily detected in urine samples.
The original peptide biomarkers were designed to be detected based on small, manipulated variations in their masses using mass spectrometry. This kind of instrumentation may not be available in resource-poor environments, so researchers can use DNA barcodes that can be read using his CRISPR technology to analyze them more easily and affordably. I started developing sensors.
For this approach to work, researchers had to use chemical modifications called phosphorothioates to prevent circulating DNA reporter barcodes from being degraded in the blood. This modification has already been used to improve the stability of the latest RNA vaccines, allowing them to survive longer in the body.
Similar to peptide reporters, each DNA barcode is attached to a nanoparticle by a linker that is cleaved by specific proteases. In the presence of that protease, DNA molecules are released to circulate freely and eventually into urine. In this study, the researcher used two different types of nanoparticles. tumor site.
When the sensor is secreted into urine, the sample can be analyzed using a strip of paper that recognizes a reporter that is activated by a CRISPR enzyme called Cas12a. If a specific DNA barcode is present in the sample, Cas12a amplifies the signal so that it can be seen as a dark strip on paper tests.
Particles can be designed to carry many different DNA barcodes, each detecting a different type of protease activity, enabling ‘multiplexed’ sensing. Using more sensors increases both sensitivity and specificity, allowing the test to more easily distinguish between tumor types.
sign of illness
In tests in mice, the researchers showed that a panel of five DNA barcodes could accurately distinguish between tumors that first developed in the lungs and tumors formed by colorectal cancer cells that metastasized to the lungs. rice field.
“Our goal here is to build disease signatures so that these barcode panels can be used not only to read disease, but also to classify disease and identify different cancer types. to see if it is,” Hao said.
The researchers anticipate the need to use five or more barcodes for use in humans, due to the large number of patient tumor types. To reach that goal, in collaboration with researchers at MIT and his Broad Institute at Harvard, led by Harvard professor Pardis Sabeti, microfluidics that can be used to read up to 46 different DNA barcodes from a single sample are being developed. I made a chip.
This type of test can be used not only to detect cancer, but also to measure how well a patient’s tumor responds to treatment and whether it has recurred after treatment. Researchers are currently working on further developing the particles with the goal of testing them in humans. The company Bhatia co-founded, his Glympse Bio, conducted a Phase 1 clinical trial of an earlier version of the urine diagnostic particles and found them to be safe for patients.
Original: A simple paper test enables early diagnosis of cancer
Than: Massachusetts Institute of Technology | Boston University | Broad Institute | Harvard University
