Once adapted for humans, this type of sensor could be used to determine how aggressive a tumor is and help doctors choose the best treatment, says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science and a member of MIT's Koch Institute for Integrative Cancer Research.
Bhatia and Polina Anikeeva, the Class of 1942 Associate Professor of Materials Science and Engineering, are the senior authors of the paper, which appears in the journal Nano Letters. The paper's lead authors are Koch Institute postdoc Simone Schurle and graduate student Jaideep Dudani.
In the new study, the researchers wanted to adapt the sensors so that they could report on the traits of tumors in a known location. To do that, they needed to ensure that the sensors were only producing a signal from the target organ, unaffected by background signals that might be produced in the bloodstream. They first designed sensors that could be activated with light once they reached their target. That required the use of ultraviolet light, however, which doesn't penetrate very far into tissue.
"We started thinking about what kinds of energy we might use that could penetrate further into the body," says Bhatia, who is also a member of MIT's Institute for Medical Engineering and Science.
To achieve that, Bhatia teamed up with Anikeeva, who specializes in using magnetic fields to remotely activate materials. The researchers decided to encapsulate Bhatia's protease-sensing nanoparticles along with magnetic particles that heat up when exposed to an alternating magnetic field. The field is produced by a small magnetic coil that changes polarity some half million times per second.
"It has been challenging to examine tumor-specific protease activities from patients' biofluids because these proteases are also present in blood and other organs," says Ji Ho (Joe) Park, an associate professor of bio and brain engineering at the Korea Advanced Institute of Science and Technology.
Cancer treatments based on proteases, now in clinical trials, consist of antibodies that target a tumor protein but have "veils" that prevent them from being activated before reaching the tumor. The veils are cleaved by proteases, so this therapy would be most effective for patients with high protease levels.
The study was funded in part by the Ludwig Center for Molecular Oncology, a Koch Institute Support Grant from the National Cancer Institute, and a Core Center Grant from the National Institute of Environmental Health Sciences.