Macrophage specific magnetic-fluorescent nanoprobes

描述（由申请人提供）：目前认为再狭窄涉及血管重塑和内膜增生的组合;但支架植入术实际上消除了重塑的作用。对再狭窄驱动机制的理解仍不完整。药物洗脱支架的最新发展显示出了希望，但关于预防再狭窄的最佳靶点还需要确定。平滑肌细胞增殖是内膜增生的关键步骤，许多药物洗脱支架旨在抑制平滑肌细胞生长，但这些支架的成功率不一致。已知巨噬细胞的积聚是再狭窄的初始步骤，并且巨噬细胞的积聚与平滑肌细胞增殖的活化之间可能存在联系，但这难以在体内研究。阐明再狭窄的细胞和分子驱动力将有助于我们制定预防措施。我们的目标是开发无毒的纳米成像探针的再狭窄，可检测的磁共振和荧光成像。本项目的最终目标是应用无创成像方法研究炎症在体内再狭窄中的作用。这些探针将在具有磁性掺杂外壳的硅纳米颗粒上进行梳理，并将通过巨噬细胞清道夫受体靶向巨噬细胞。这些受体在巨噬细胞上大量存在，但在正常血管壁的管腔表面上不存在。已知巨噬细胞在早期病变中积累。我们将使用MRI和光学成像技术相结合，以关联免疫细胞募集与随后的再狭窄。硅纳米颗粒的使用代表了对发光纳米颗粒探针技术的显著改进，因为硅是无毒的，而大多数当前可用的发光纳米颗粒基于含镉化合物。

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.