April 13, 2012 — Researchers at The Ohio State University (OSU) Wexner Medical Center have successfully used nanotechnology to target a protein that plays a key role in atherosclerosis and inflammation. Researchers say the study is an important advance toward using immunotherapy to simultaneously diagnose and treat cardiovascular disease. The research is published in the April edition of the journal Arteriosclerosis, Thrombosis and Vascular Biology.
Myeloid-related protein 8/14 complex (Mrp8/14) regulates vascular inflammation in atherosclerosis and its presence is readily detectable in human and animal atherosclerotic plaques.
“Because it is so highly expressed in plaque, we wanted to target Mrp8/14 for magnetic resonance imaging (MRI) as a way to assess and estimate disease progression,” says Andrei Maiseyeu, a researcher at OSU’s Dorothy M. Davis Heart and Lung Research Institute.
Maiseyeu and his team engineered a new nanoprobe, which is a tiny device that helps detect very small structures on a cellular level. The nanoprobe binds to Mrp 8/14 and contains gadolinium contrast agent to use with MRI. Building on their previous research, the team used nanoparticles made of phospholipids and Mrp antibodies, both of which have an anti-inflammatory effect. These nanoparticles accumulate, allowing researchers to better locate and assess the plaque.
They tested the nanoprobe in mice with atherosclerosis and in mice that were Mrp deficient. The results showed the anti-Mrp nanoprobe enhanced imaging of the aortic wall nearly five-fold in mice with atherosclerosis. Additionally, researchers reported the image clarity, or contrast-to-noise ratio, improved 22-fold. There was no enhancement in the images from the Mrp deficient mice.
“We were a little surprised by how pronounced the image enhancement was using the nanoprobe, and it gives us great hope,” says Maiseyeu. “There are many antibody therapies for cancer, but none so far for cardiovascular disease. We will study this further in an effort to establish immunotherapy for cardiovascular disease.”
The team also noted the anti-Mrp probe neutralized the inflammatory effects of Mrp8/14. Maiseyeu says this paves the way for developing a diagnostic device that also has therapeutic benefit, also called theranostic technology.
“Theranostics has potential to streamline patient care with more efficient diagnosis and treatment, and more precise imaging of disease,” says Sanjay Rajagopalan, director of vascular research at OSU’s Wexner Medical Center and senior author on the study. “It’s an exciting and popular area to explore.”
The team is now developing a nanoprobe with an antibody that is more specific to humans for testing in human atherosclerotic tissue. Other Ohio State researchers involved in the study include: Georgeta Mihai, Qinghua Sun, Jeffrey Deiuliis, Cuiqing Liu and Marcus Badgeley. The research was funded by the National Heart, Lung and Blood Institute and the American Heart Association.
For more information: www.medicalcenter.osu.edu