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Analytical Chemistry

Pancreatic cancer biomarker bolsters nanoparticle-based diagnostic

Speedy sensor detects vesicles released by tumors in tiny drops of blood

by Matt Davenport
February 8, 2017 | A version of this story appeared in Volume 95, Issue 7

Arizona State University’s Ye (Tony) Hu and his colleagues have delivered what they hope will be a double dose of good news for detecting pancreatic cancer. Pancreatic cancer is one of the leading causes of cancer deaths because it often goes undetected in early stages, according to the Mayo Clinic.

The researchers report a rapid and inexpensive nanoparticle-based diagnostic fueled, in part, by a biomarker on the surface of vesicles released by pancreatic tumors (Nat. Biomed. Eng. 2017, DOI: 10.1038/s41551-016-0021).

As tumors develop, they release microscopic vesicles into a person’s blood. If biosensors could isolate and identify these vesicles, researchers could potentially catch cancer early by pricking a person’s finger and analyzing blood droplets. This process would be easier and less costly than more conventional biopsies or positron emission tomography scans, Hu says.

But all cells release vesicles, and determining whether those vesicles come from healthy cells or cancerous tissue is a challenge, he explains. Now he and his colleagues have found that vesicles released by pancreatic cancer tumors overexpress the surface protein ephrin type-A receptor 2, or EphA2.

The researchers focused on EphA2 because of evidence collected by other cancer researchers and a computerized proteomic analysis. In this study, their diagnostic tool helps solidify the protein as a biomarker of tumor-derived vesicles.

The biosensor consists of a glass slide divided into wells decorated with antibodies that capture extracellular vesicles by binding to a protein biomarker on the particles. Each well also contains gold nanorods and gold nanospheres that scatter light differently and shine red and green, respectively, under a microscope.

The rods are coated with antibodies specific to vesicles from pancreatic cells, and the team adorned the spheres with antibodies that bind to EphA2. Vesicles from pancreatic cancer cells thus bind both gold particle shapes. Crowding the rods and spheres onto the same vesicle causes the combo to glow yellow.

The team showed that this sensor differentiates between blood from healthy people, people with pancreatic cancer, and people with pancreatic inflammation. The latter condition is often confused with cancer in tests that use other biomarkers, Hu explains. The sensor requires minimal sample preparation, and its reagents are comparable in cost to other immunoassay techniques, notably enzyme-linked immunosorbent assay (ELISA), the team reports. The sensor also works with samples as small as 1 µL, while ELISA needs more than 100 µL.

Rajesh Sardar, who develops nanosensors at Indiana University-Purdue University Indianapolis, says the new tool is exciting and transformative. “This simple, optical-based technique has the potential to screen patient samples much faster than ELISA or polymerase chain reaction,” he adds.

Pathologist Anirban Maitra agrees that the technology is promising and innovative. He works at the MD Anderson Cancer Center, as do some of Hu’s coworkers, although Maitra was not involved with the study.

Maitra, however, points out that the study was not blinded and each group was small, with about 50 people. Data in smaller studies such as this tend to look good, he says. “Validation in larger, blinded sample sets becomes imperative,” he says. “I am hopeful that the PI and his team will expand their studies.”

A schematic shows how a new biosensor is designed to detect vesicles from pancreatic cancer tumors, along with a photo of an optical readout from the device.
Credit: Nat. Biomed. Eng.
In a new sensor, a trio of antibodies helps capture and decorate vesicles from pancreatic cancer cells with gold nanorods (red) and nanospheres (green), causing the vesicles to glow yellow.


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