In experiments involving mice, the researchers successfully measured the activity of five different cancer-associated proteases simultaneously.
Engineers at the Massachusetts Institute of Technology (MIT) in the United States have developed tiny nanoparticles capable of detecting cancer from a simple urine sample. The experimental technology can identify the activity of multiple cancer-related proteins, distinguish between different tumor types, and even indicate whether a cancer has metastasized, according to a study published in Nature Nanotechnology.
Unlike conventional blood tests that search for naturally occurring tumor biomarkers, which are often present in extremely low concentrations during the earliest stages of disease — the new system relies on synthetic biomarkers engineered to amplify biological signals generated by tumors.
How The Test Works
The nanoparticles circulate through the bloodstream until they encounter a tumor. Their surface is coated with specially designed peptides that are cut by enzymes known as proteases, which are highly active in many cancers and play a crucial role in tumor growth, invasion and metastasis.
When these peptides are cleaved, they release tiny DNA barcodes that are filtered by the kidneys and appear in urine.
Each barcode corresponds to a specific protease, creating a molecular fingerprint that reveals the biological characteristics of the tumor.
Rather than requiring expensive laboratory equipment such as mass spectrometers, the MIT team designed the DNA barcodes to be detected using CRISPR-Cas12a, a gene-editing enzyme that can also function as an extremely sensitive molecular detector.
The urine is applied to a paper strip similar to a rapid COVID-19 test. If a particular DNA barcode is present, Cas12a amplifies the signal and produces a visible dark band, allowing results to be read without sophisticated laboratory instruments.
Distinguishing Between Cancers
In experiments involving mice, the researchers successfully measured the activity of five different cancer-associated proteases simultaneously.
Using a panel of five DNA barcodes, they were able to distinguish primary lung tumors from colorectal cancers that had spread to the lungs, demonstrating that the technology can provide information not only about the presence of cancer but also about its origin.
The researchers estimate that the platform can ultimately recognize dozens of distinct molecular signatures in a single urine sample, greatly expanding its diagnostic potential.
Designed For Low-Resource Settings
One of the project’s main goals is to make advanced cancer diagnostics available outside specialized hospitals.
Because the test relies on inexpensive nanoparticles and paper strips rather than complex imaging systems or laboratory analyzers, it could eventually provide rapid, point-of-care cancer screening in low- and middle-income countries, rural clinics, or even patients’ homes.
“The vision is to democratize access to cancer diagnostics,” the researchers said in an MIT news release.
Building on Years of Research
The study represents the latest step in a decade-long effort by the laboratory of Prof. Sangeeta Bhatia at MIT, which pioneered the concept of synthetic urinary biomarkers.
Earlier generations of the technology relied on laboratory-based mass spectrometry to identify released biomarkers. The new version replaces that expensive equipment with CRISPR-based detection, making the system significantly cheaper and easier to deploy.
Researchers also expanded the number of detectable biomarkers, allowing multiple cancer-associated enzymes to be analyzed simultaneously rather than relying on a single molecular target.
Why Early Detection Matters
Cancer remains one of the world’s leading causes of death. According to the World Health Organization (WHO), cancer caused nearly 10 million deaths worldwide in 2022, while roughly one in five people will develop cancer during their lifetime.
Many cancers become highly treatable when detected before they spread, yet early diagnosis remains difficult because tumors often produce too few detectable biomarkers in blood during their initial stages.
By amplifying these otherwise faint biological signals, synthetic biomarkers could make earlier diagnosis possible while reducing the need for invasive biopsies.
MIT’s approach is part of a broader effort to develop non-invasive cancer diagnostics.
Researchers are also investigating:
Liquid biopsies, which analyze fragments of tumor DNA (circulating tumor DNA, or ctDNA) in blood to detect cancers and monitor treatment response. Several liquid-biopsy tests have already entered clinical use for specific applications, although detecting very early cancers remains challenging.
Urine-based tests for bladder, prostate and kidney cancers that identify tumor DNA, RNA or proteins. Most existing urine tests, however, are designed for particular cancer types rather than serving as a universal platform.
Multi-cancer early detection (MCED) blood tests that combine DNA methylation patterns with artificial intelligence to identify dozens of cancer types from a single blood sample. Large clinical trials are still underway to determine their impact on population screening.
The MIT technology differs by actively generating synthetic biomarkers instead of relying solely on naturally occurring ones, potentially increasing sensitivity for very small tumors.
Next Steps
The technology is still in the preclinical stage and has so far been tested only in laboratory mice. Human clinical trials will be needed to determine its safety, accuracy and effectiveness before it could become available to patients.
The MIT team plans to expand the library of DNA barcodes so the system can recognize a much wider range of cancers and disease stages.
The research involved scientists from MIT, Harvard University, and several collaborating institutions, and was supported by the U.S. National Cancer Institute, the National Institute of Environmental Health Sciences, the Marble Center for Cancer Nanomedicine, and other funding organizations.