Early detection of pancreatic cancer closer thanks to multifunctional nanoparticles

Pancreatic cancer has a devastatingly low survival rate (less than 5 percent after 5 years) because it is usually diagnosed at an advanced stage. The initial symptoms, such as pain, jaundice, or weight loss, often do not allow the disease to be caught early enough for surgery and chemotherapy to be effective.

Now, Emory University researchers, led by Lily Yang, M.D., Hui Mao, Ph.D., and Shuming Nie, Ph.D., have created tools for the early diagnosis of pancreatic cancer by attaching a molecule that binds specifically to pancreatic cancer cells to iron oxide nanoparticles that are clearly visible under magnetic resonance imaging (MRI). Tested in mice with implanted human tumors, the particles also can be seen by scanning the mice with a specialized camera because the particles are studded with near-infrared dyes. The properties of the nanoparticles are described in the journal Gastroenterology. Dr. Nie is the principal investigator, and Dr. Yang is a member of the Emory-Georgia Tech Nanotechnology Center for Personalized and Predictive Oncology.

"This work is an early demonstration that nanoparticles can be developed to target pancreatic cancer, opening new opportunities in detecting and treating tumors of low survival rates," said Dr. Nie. "We believe these nanoparticles could be useful tools for detection and localization before surgery, detection of tumor margins and metastases during surgery, and monitoring of the response to therapy," added Dr.Yang. "We are working on multifunctional nanoparticles that could both detect pancreatic tumors by molecular imaging and deliver therapeutic agents in a targeted fashion."

The iron oxide particles have a core that is 10 nanometers in diameter, with a polymer coating. The molecule that allows the particles to discriminate between pancreatic cancer cells and healthy cells is an engineered small protein based on a natural protein found in humans, urokinase plasminogen activator (uPA), which binds to its receptor (uPAR) on cancer cells.

The investigators note that uPA is useful in discriminating tumor cells from regular pancreatic cells irritated by chronic pancreatitis, a challenging task in clinical diagnosis. They found that particles coated with a fragment of uPA are taken up by pancreatic cancer cells and not by normal pancreatic tissue. Tumor endothelial cells, which line blood vessels, also take up the particles, and a low signal is seen in liver and spleen.

Tumors as small as 1 millimeter across can be detected by MRI or optical imaging. The technology now needs to be refined so that it is ready to test in patients. Groups of patients that are at increased risk of pancreatic cancer, such as those with inherited cancer risk factors, chronic pancreatitis, or new-onset diabetes, could benefit.

This work, which is detailed in the paper "Molecular imaging of pancreatic cancer in an animal model using targeting multifunctional nanoparticles," was supported by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. An investigator from Ocean NanoTech, LLC, also participated in this study. An abstract is available at the journal's Web site. View abstract


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