Engineered polymeric nanoparticles for receptor-targeted blockage of oxidized low density lipoprotein uptake and atherogenesis in macrophages
Engineered polymeric nanoparticles for receptor-targeted blockage of oxidized low density lipoprotein uptake and atherogenesis in macrophages
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DOI：
10.1021/bm0600872
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发表时间：
2006-06-01
影响因子：
6.2
通讯作者：
Moghe, Prabhas V.
中科院分区：
文献类型：
--
作者：
Chnari, Evangelia;Nikitczuk, Jessica S.;Moghe, Prabhas V.
预防免疫细胞摄取修饰的低密度脂蛋白（LDL）（炎症和动脉粥样硬化形成的主要触发因素）的策略受到控制LDL受体介导的摄取的复杂界面因素的挑战。我们研究了一种新的方法，基于一个家庭的“nanoblockers”，旨在研究的作用，电荷呈现，和架构抑制高度氧化的低密度脂蛋白（hoxLDL）在巨噬细胞的摄取。纳米阻断剂是含有粘酸、月桂基氯化物和聚（乙二醇）的大分子，其自组装成15-20 nm的纳米颗粒。我们报告说，胶束配置的大分子和组合显示的阴离子（羧酸盐）基团的疏水区域的纳米阻滞剂引起的最有效的抑制hoxLDL的摄取IC 21巨噬细胞。纳米阻断剂主要靶向SR-A和CD 36，主要的清道夫受体，并在细胞因子分泌、胆固醇积累和“泡沫细胞”形成的程度方面调节细胞的“致动脉粥样硬化”表型。这些研究突出了合成工程纳米阻滞剂对氧化LDL摄取的承诺。
Strategies to prevent the uptake of modified low density lipoproteins (LDLs) by immune cells, a major trigger of inflammation and atherogenesis, are challenged by complex interfacial factors governing LDL receptor-mediated uptake. We examine a new approach based on a family of "nanoblockers", which are designed to examine the role of size, charge presentation, and architecture on inhibition of highly oxidized LDL (hoxLDL) uptake in macrophages. The nanoblockers are macromolecules containing mucic acid, lauryl chloride, and poly(ethylene glycol) that self-assemble into 15-20 nm nanoparticles. We report that the micellar configuration of the macromolecules and the combined display of anionic (carboxylate) groups in the hydrophobic region of the nanoblockers caused the most effective inhibition in the uptake of hoxLDL by IC21 macrophages. The nanoblockers primarily targeted SR-A and CD36, the major scavenger receptors and modulated the "atherogenic" phenotype of cells in terms of the degree of cytokine secretion, accumulation of cholesterol, and "foam cell" formation. These studies highlight the promise of synthetically engineered nanoblockers against oxidized LDL uptake.