Category: Micro- and Nanotechnologies
Cardiovascular disease is the leading cause of mortality in the United States. Atherosclerosis, a major source of cardiovascular disease, is often asymptomatic until the activation of thrombosis and the rupture of enlarged plaques, resulting in acute coronary syndromes and sudden cardiac arrest. Traditionally, atherosclerosis is evaluated using luminal stenosis by anatomical imaging using angiography or ultrasound. However, these methods can only determine severe narrowing of the arterial wall, and the progression of atherosclerosis is not observed. Magnetic resonance imaging (MRI) is a noninvasive nuclear imaging technique with high spatial resolution and excellent soft tissue contrast. As MRI does not require the use of ionizing radiation, repetitive morphological follow-up is possible without compromising safety. Peptide-based nanomaterials provide several potential advantages over conventional small molecules as the peptide enhances multivalent binding to cell-surface receptors, which can increase delivery efficacy to tissue-specific sites. Previously, we have incorporated the fibrin-binding peptide, CREKA, into peptide amphiphile micelles (PAMs) for targeting thrombosis in atherosclerosis. Here, we have developed a hybrid nanoparticle platform (CREKA-Fe3O4-PAM) that consists of a highly crystalline inorganic iron oxide core encapsulated with organic fibrin-targeting peptide amphiphiles for enhanced MRI detection of plaques most at risk of rupture. CREKA-Fe3O4-PAMs combine the beneficial features of both inorganic (small particle size, improved stability, and enhanced permeability) and organic components (biocompatibility and biodegradability). These hybrid nanoparticles are self-assembled and are ~20 nm in diameter, confirmed by dynamic light scattering. Transmission electron microscopy images displayed the formation of uniform, spherical nanoparticles. In vitro, CREKA-Fe3O4-PAMs were found to be biocompatible in human aorta endothelial cells. Moreover, CREKA-Fe3O4-PAMs bound to clots three times higher than that of non-targeting counterpart nanoparticles, and in vitro MR imaging studies confirmed the effective delivery of contrast agent to clots. This hybrid nanoplatform provides the foundation of a non-invasive, vital approach for early screening and detection of thrombosis in preclinical models of atherosclerosis.
Christopher Poon– Postdoctoral Scholar, University of Southern California, Los Angeles, CA
University of Southern California
Los Angeles, CA
Christopher Poon received his B.S. in Chemistry and Biochemistry from University of Washington and his Ph.D. in Chemistry from University of Chicago under the direction of Professor Wenbin Lin, where his focus was on the development of nanoscale coordination polymers that co-deliver multiple therapeutics for combination therapy of cancer. Chris is currently a postdoctoral scholar in Biomedical Engineering at University of Southern California, where he is working with Professor Eun Ji Chung on developing novel therapeutic peptide amphiphile micelles for the treatment of atherosclerosis. His research interests include nanomedicine, drug delivery, drug safety, and immunotherapy.