利用模块化多功能胶束靶向治疗动脉粥样硬化。
Targeting atherosclerosis by using modular, multifunctional micelles.
作者信息
Peters David, Kastantin Mark, Kotamraju Venkata Ramana, Karmali Priya P, Gujraty Kunal, Tirrell Matthew, Ruoslahti Erkki
机构信息
Vascular Mapping Center, Burnham Institute for Medical Research, University of California, Santa Barbara, 3119 Biology II Building, CA 93106-9610, USA.
出版信息
Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9815-9. doi: 10.1073/pnas.0903369106. Epub 2009 Jun 1.
Subtle clotting that occurs on the luminal surface of atherosclerotic plaques presents a novel target for nanoparticle-based diagnostics and therapeutics. We have developed modular multifunctional micelles that contain a targeting element, a fluorophore, and, when desired, a drug component in the same particle. Targeting atherosclerotic plaques in ApoE-null mice fed a high-fat diet was accomplished with the pentapeptide cysteine-arginine-glutamic acid-lysine-alanine, which binds to clotted plasma proteins. The fluorescent micelles bind to the entire surface of the plaque, and notably, concentrate at the shoulders of the plaque, a location that is prone to rupture. We also show that the targeted micelles deliver an increased concentration of the anticoagulant drug hirulog to the plaque compared with untargeted micelles.
发生在动脉粥样硬化斑块管腔表面的细微凝血现象为基于纳米颗粒的诊断和治疗提供了一个新靶点。我们开发了模块化多功能胶束,其在同一颗粒中包含一个靶向元件、一个荧光团,以及根据需要添加的药物成分。通过与凝血血浆蛋白结合的五肽半胱氨酸 - 精氨酸 - 谷氨酸 - 赖氨酸 - 丙氨酸,在喂食高脂饮食的载脂蛋白E基因敲除小鼠中实现了对动脉粥样硬化斑块的靶向。荧光胶束与斑块的整个表面结合,值得注意的是,它们集中在斑块易于破裂的肩部。我们还表明,与非靶向胶束相比,靶向胶束能将更高浓度的抗凝药物水蛭素输送到斑块中。