Nanoparticle Sensor Array Emerges as Potential New Diagnostic Tool

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Researchers at Brigham and Women’s Hospital say they are taking advantage of a unique phenomenon of nanoparticles to develop a test for early detection of different types of diseases, including cancer. Through previous investigations, Morteza Mahmoudi, PhD, now a biomedical investigator in the department of anesthesiology, perioperative and pain medicine, and colleagues have shown that biomolecules in the blood of healthy individuals and patients form various corona profiles around nanoparticles.

In a new study (“Disease-specific protein corona sensor arrays may have disease detection capacity”) published in the Royal Society of Chemistry’s journal Nanoscale Horizons, Mahmoudi and the team presented evidence that these coronas are personalized and precise, with different compositions or patterns in people with cancers. They have developed a sensor array that has been tested on blood samples, both from people diagnosed with five different types of cancer as well as purportedly healthy people who went on to have a cancer diagnosis several years later. The team’s goal is to develop an early detection test that could be used in the clinic to identify those at risk of cancer and other diseases.

The earlier any catastrophic disease (e.g., cancer) is diagnosed, the more likely it can be treated, providing improved patient prognosis, extended survival, and better quality of life. In early 2014, we revealed that various types of disease can substantially affect the composition/profile of protein corona (i.e., a layer of biomolecules that forms at the surface of nanoparticles upon their interactions with biological fluids),” the investigators wrote.

“Here, by combining the concepts of disease-specific protein corona and sensor array technology we developed a platform with disease detection capacity using blood plasma. Our sensor array consists of three cross-reactive liposomes, with distinct lipid composition and surface charge. Rather than detecting a specific biomarker, the sensor array provides pattern recognition of the corona protein composition adsorbed on the liposomes. As a feasibility study, sensor array validation was performed using plasma samples obtained from patients diagnosed with five different cancer types (i.e., lung cancer, glioblastoma, meningioma, myeloma, and pancreatic cancer) and a control group of healthy donors. Although no single corona composition is specific for any one cancer type, overlapping but distinct patterns of the corona composition constitute a unique `fingerprint’ for each type of cancer (with a high classification accuracy, i.e., 99.4%).

“To finally probe the capacity of this sensor array for early detection of cancers, we used cohort plasma obtained from healthy people who were subsequently diagnosed several years after plasma collection with lung, brain, and pancreatic cancers. Our results suggest that the disease-specific protein corona sensor array will not only be instrumental in the screening, detection, and identification of diseases, but may also help identify novel protein pattern markers whose role in disease development and/or disease biology has not been appreciated so far.”

“The goal here is to develop a strategy to help people get better information about their health. Today, in the clinic, we have ways to measure lipids and predict risk of cardiovascular disease, but limited ways for cancer,” said Mahmoudi, the paper’s corresponding author and former director of the nanobio interactions laboratory at Tehran University of Medical Sciences where he began this work in 2014. “If everything goes well, we hope our work will lead to a screening test for the earliest signs of cancer.”

Although promising, as with other diagnostic approaches, the team’s preliminary results will need to be validated in a larger number of people to make sure the test not only works but also provides accurate diagnostic information. Mahmoudi and his colleagues are also interested in applying the technology beyond cancer to diagnose other diseases at an early stage.

“The only reason I’m in science is to do something that can help patients,” continued Mahmoudi. “When I see predictions about cancer, the number of new cases each year and its global burden, it excites me to think that our multidisciplinary expertise in nanobio interfaces, sensor array, and advanced statistics may offer a way to help. There is so much potential here and we are working to tap into it.”

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