Macrophage specific magnetic-fluorescent nanoprobes

描述(申请人提供)：再狭窄现在被认为涉及血管重塑和内膜增生的组合；但支架置入术实际上消除了重塑的影响。对于导致再狭窄的机制的了解仍不完全。药物洗脱支架的最新发展前景看好，但对于预防再狭窄的最佳靶点，仍有许多需要确定。血管内皮细胞的增殖是血管内膜增生的关键步骤，许多药物洗脱支架被用于抑制血管内膜细胞的生长，但这些支架的成功与否并不一致。巨噬细胞积聚是再狭窄发生的第一步，巨噬细胞积聚与激活血管平滑肌细胞增殖之间可能存在联系，但这一点很难在体内进行研究。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颗粒再狭窄成像探针，可以通过磁共振和荧光成像检测到。该项目的最终目标是应用非侵入性成像方法来研究炎症在体内再狭窄中的作用。这些探针将被戏弄在带有磁性掺杂外壳的硅纳米颗粒上，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不存在。已知巨噬细胞在早期病变中积聚。我们将结合使用MRI和光学成像技术来将免疫细胞募集与随后的再狭窄联系起来。硅纳米颗粒的使用代表了发光纳米颗粒探测技术的重大改进，因为硅是无毒的，而目前可用的大多数发光纳米颗粒是基于含镉的化合物。

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.