Core hydrophobicity tuning of a self-assembled particle results in efficient lipid reduction and favorable organ distribution.
Core hydrophobicity tuning of a self-assembled particle results in efficient lipid reduction and favorable organ distribution.
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DOI：
10.1039/c7nr06295h
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发表时间：
2017-12-21
期刊：
影响因子：
6.7
通讯作者：
Dhar S
中科院分区：
文献类型：
--
作者：
Banik B;Wen R;Marrache S;Kumar A;Kolishetti N;Howerth EW;Dhar S
动脉粥样硬化是美国最致命的疾病，是由于胆固醇过度沉积和胆固醇清除过程受损而在动脉中形成斑块而引起的。高密度脂蛋白 (HDL)，俗称“好胆固醇”，是天然存在的纳米级颗粒，与载脂蛋白一起用于维持体内胆固醇稳态。胆固醇从动脉中富含脂肪的巨噬细胞流出，以及细胞内脂质运输，将胆固醇输送到肝细胞的线粒体进行新陈代谢，对于维持体内健康的脂质水平起着关键作用。我们设计了一个由九种线粒体靶向聚合物-脂质混合纳米粒子 (NP) 组成的库，由完全合成但可生物降解的成分组成，能够执行类似 HDL 的功能。使用该库，我们优化了一种优异的线粒体靶向 NP 候选物，它可以显示出良好的器官分布、治疗潜力和无毒特性。确定了两种具有最佳 NP 尺寸、zeta 电位以及胆固醇结合和释放特性的靶向 NP 制剂。这两种纳米粒子的降脂和抗氧化特性表现出去除胆固醇的能力。对载脂蛋白 E 敲除 (apoE−/−) 小鼠进行的靶向 NP 制剂的体内治疗评估表明，与非靶向 NP 相比，具有降脂和抗炎特性。这种合成的靶向纳米颗粒具有参与细胞外和细胞内胆固醇转运的潜在能力，可能会增强对心脏病的治疗干预。用于降低脂质和动脉粥样硬化的自我治疗线粒体靶向纳米颗粒的优化。
Atherosclerosis, the deadliest disease in the United States, arises due to the building up of plaques in the arteries as a result of excessive cholesterol deposition and impaired cholesterol removal process. High density lipoproteins (HDL), popularly known as “good cholesterol”, are naturally occurring nano-sized particles that, along with apolipoproteins are deployed to maintain cholesterol homeostasis in the body. Both cholesterol efflux, from the fat-laden macrophages in the arteries, and intracellular lipid transport, to deliver cholesterol to the mitochondria of liver cells for metabolism, hold key responsibilities to maintain healthy lipid levels inside the body. We designed a library of nine mitochondria targeted polymer-lipid hybrid nanoparticles (NPs), comprised of completely synthetic yet biodegradable components, that are capable of performing HDL-like functions. Using this library, we optimized a superior mitochondria targeted NP candidate which can show favourable organ distribution, therapeutic potential, and non-toxic properties. Two targeted NP formulations with optimum NP size, zeta potential, and cholesterol binding and release properties were identified. Lipid reduction and anti-oxidative properties of these two NPs demonstrated cholesterol removal ability. In vivo therapeutic evaluation of targeted-NP formulation in apolipoprotein E knockout (apoE−/−) mice indicated lipid reduction and anti-inflammatory properties compared to non-targeted NPs. This synthetic targeted NP with potential abilities to participate in both extra- and intracellular cholesterol transport might potentiate therapeutic interventions for heart diseases. Optimization of a self-therapeutic mitochondria targeted nanoparticle for lipid reduction and atherosclerosis.
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影响因子：
8.7
作者：
Jones, NL;Reagan, JW;Willingham, MC
通讯作者：
Willingham, MC
影响因子：
4.8
作者：
Chen, Wei;Jarzyna, Peter A.;Fayad, Zahi A.
通讯作者：
Fayad, Zahi A.
影响因子：
4.7
作者：
Barazza, Alessandra;Blachford, Courtney;Fisher, Edward A.
通讯作者：
Fisher, Edward A.
DOI：
10.1073/pnas.1301929110
发表时间：
2013-06-04
影响因子：
11.1
作者：
Marrache, Sean;Dhar, Shanta
通讯作者：
Dhar, Shanta
影响因子：
6.5
作者：
Luthi AJ;Lyssenko NN;Quach D;McMahon KM;Millar JS;Vickers KC;Rader DJ;Phillips MC;Mirkin CA;Thaxton CS
通讯作者：
Thaxton CS