Macrophage specific magnetic-fluorescent nanoprobes

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Restenosis is now understood to involve a combination of vascular remodeling and intimal hyperplasia; but stenting virtually eliminates the contribution from remodeling. The understanding of the mechanisms driving restenosis remains incomplete. The recent development of drug eluting stents shows promise but much needs to be determined regarding the best targets to prevent restenosis. Proliferation of smooth muscle cells is a key step in intimal hyperplasia and a number of drug-eluting stents are directed at prohibiting smooth muscle cell growth, however these have met with inconsistent success. Accumulation of macrophages is known to be an initial step in restenosis and there may be a connection between the accumulation of macrophages and the activation of smooth muscle cell proliferation but this is difficult to study in vivo. Elucidating the cellular and molecular driving forces in restenosis will help us to develop preventative measures. Our goal is to develop nontoxic nanoparticle imaging probes of restenosis that are detectable by both magnetic resonance and fluorescence imaging. The ultimate goal of this project is to apply noninvasive imaging methods to investigate the role of inflammation in restenosis in vivo. The probes will be teased on silicon nanoparticles with magnetically doped shells, and will be targeted to macrophages through macrophage scavenger receptors. These receptors are found in high numbers on macrophages, but not on the lumenal surface of normal vessel walls. Macrophages are known to accumulate in early lesions. We will use a combination of MRI and optical imaging techniques to correlate immune cell recruitment with subsequent restenosis. The use of silicon nanoparticles represents a significant improvement to luminescent nanoparticle probe technology in that silicon is not toxic, while most currently available luminescent nanoparticles are based on cadmium containing compounds.