May 5, 2009
Iron Nanoparticle Tools Could Detect Pancreatic Cancer Earlier
Pancreatic cancer has a devastatingly low survival rate (less than five percent after five 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.
Emory researchers have created tools for early diagnosis of pancreatic cancer by attaching a molecule that binds specifically to pancreatic cancer cells to tiny "nanoparticles" made of iron oxide.
The iron makes the particles clearly visible under magnetic resonance imaging (MRI). Tested in mice with implanted human tumors, the particles can also be seen by scanning the mice with a specialized camera because the particles are studded with near infrared dyes.
The nanoparticles' properties are described in the May issue of the journal Gastroenterology.
The research was a collaboration between Lily Yang, MD, associate professor of surgery at Emory University School of Medicine, Hui Mao, PhD, associate professor of radiology at Emory, and Shuming Nie, PhD, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.
Additional contributions came from Charles Staley, MD, and William Wood, MD, both professors of surgery at Emory School of Medicine, and from Y. Andrew Wang of Ocean Nanotech LLC.
"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," says 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 the response to therapy," Yang says. "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 authors note that uPA is useful in discriminating tumor cells from regular pancreas cells irritated by chronic pancreatitis, a challenging task in clinical diagnosis.
Particles coated with a fragment of uPA are taken up by pancreatic cancer cells and not by normal pancreatic tissues, they found. 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 one 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.
Yang, L. et al Molecular Imaging of Pancreatic Cancer in an Animal Model Using Targeted Multifunctional Nanoparticles. Gastroenterology 136, 1514-1525 (May 2009)
The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include schools of medicine, nursing, and public health; Yerkes National Primate Research Center; the Emory Winship Cancer Institute; and Emory Healthcare, the largest, most comprehensive health system in Georgia. The Woodruff Health Sciences Center has a $2.3 billion budget, 17,000 employees, 2,300 full-time and 1,900 affiliated faculty, 4,300 students and trainees, and a $4.9 billion economic impact on metro Atlanta.