Researchers at the Massachusetts Institute of Technology (MIT) have developed a catheter-based nanosensor that can detect the recurrence of bladder cancer at an earlier stage by identifying a biomarker released by tumors directly within the bladder. The technology, detailed in Nature Nanotechnology, combines carbon nanotube sensors with a rotating optical imaging device to create what researchers describe as a three-dimensional chemical imaging platform capable of locating cancer-associated biomarkers within tissue.
“It’s like a camera for molecules instead of light,” said Michael Strano, PhD, a professor of chemical engineering at MIT and senior author of the study. “If you have a billion nanosensors in an array, you can use them to make a chemical image that helps you locate their source.”
Roughly 85,000 people in the U.S. are diagnosed with bladder cancer each year, and more than half of patients experience recurrence within five years. The disease also carries among the highest lifetime treatment costs because patients require ongoing surveillance.
The new method addresses a major challenge in detecting bladder cancer recurrence, which currently relies on urinalysis to look for signs cancer has returned. Using urine for detection is hindered since biomarkers of cancer recurrence are diluted, degraded, and are often cleared shortly after they are released by the new tumor.
To address this, the MIT researchers targeted the matrix protein 22 (NMP-22), an FDA-approved biomarker for bladder cancer. While it is possible to detect NMP-22 in urine, the shortcomings of that method often mean that the cancer is often only found at a later stage of development.
To overcome this gap, the MIT team looked for a way to develop a sensor that could work inside the bladder. Their device consists of a urinary catheter coated with specialized nanosensors that detect the presence of NMP-22. A miniature rotating ball lens embedded in the catheter tip emits laser light and collects fluorescent signals generated by the nanotubes when they interact with the target biomarker.
Over the past decade, Strano’s laboratory has focused on developing carbon nanotube-based sensors that can identify specific molecules. The team customizes nanotubes for each application by applying different polymer coatings that function as “synthetic antibodies,” enabling them to bind to disease biomarkers. Previous development efforts in the lab have yielded sensors capable of detecting molecules such as hydrogen peroxide, riboflavin, and viral proteins.
For the bladder cancer application, researchers engineered a phospholipid-containing a synthetic polymer that selectively recognizes NMP-22. The project was partly motivated by earlier computational modeling conducted by the team, which suggested that placing sensors near an emerging bladder tumor could produce “a more than 50,000-fold increase in detection limit by minimizing biomarker dilution and degradation.” That finding pointed toward the potential advantages of measuring biomarkers at their source rather than after they enter urine.
In experimental testing, the platform achieved a 182-fold signal enhancement compared with biofluid sampling. The new technology was tested in multiple ways. The researchers first tested the nanosensors against six bladder cancer cell lines and healthy fibroblast cells and found distinct sensor responses associated with cancer-cell apoptosis. The team also used the chemotherapy drug gemcitabine to induce cancer cell death in vitro and monitored the resulting release of biomarkers. siRNA analysis confirmed that NMP-22 was a major contributor to the detected signals.
Researchers then evaluated the platform in porcine bladder models using a catheter coated with the specially designed nanotubes. Using a rotating ball lens system, they generated chemical maps showing the location of biomarker sources and demonstrated detection at distances up to two centimeters from the source. The researchers also reported a simulated tumor resolution of 16 square millimeters.
The chemical imaging capability is a unique attribute of the new method and the information it can provide should be very useful for treating recurrent cancer. “If you are scanning over a region of tissue, you would like to know not just that there is a signal indicating that a tumor is there, but also its location so that you can treat it or perform a biopsy,” Strano said. “Before an early-stage tumor breaks through the urothelium so that it’s visible, it’s under the surface but still emitting chemical signals that can be imaged.”
While the study focused on bladder cancer, the researchers indicated that the underlying platform may have broader applications. By replacing the nanosensors with versions designed to recognize other biomarkers, the system could potentially be adapted for additional cancers or for diseases affecting the cardiovascular or gastrointestinal systems.
“The beauty of polymer chemistry is that if we understand the molecular structures of target biomarkers and the design principles of binding sites, we can develop new sensors tailored to different diseases,” said lead author Wonjun Yim, PhD.
Future work will focus on expanding the range of detectable analytes, developing multiplexed sensor arrays, conducting omics-based biomarker validation studies, and improving optical engineering. The researchers also aim to miniaturize the imaging system and integrate the technology into cystoscopes already used in clinical practice.
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