Biofunctional Polymer Lipid Hybrid High-Density Lipoprotein Mimicking Nanoparticles Loading Anti-miR155 for Combined Antiatherogenic Effects on Macrophages

被引：37
作者：
Lu, Jing [1 ]
Zhao, Yi [1 ]
Zhou, Xiaoju [1 ]
He, Jian Hua [1 ]
Yang, Yun [1 ]
Jiang, Cuiping [1 ]
Qi, Zitong [1 ]
Zhang, Wenli [1 ]
Liu, Jianping [1 ]
机构：
[1] China Pharmaceut Univ, Dept Pharmaceut, Nanjing 211198, Jiangsu, Peoples R China
来源：
BIOMACROMOLECULES | 2017年 / 18卷 / 08期
基金：
中国国家自然科学基金;
关键词：
E-DEFICIENT MICE; TARGETED DELIVERY; RECONSTITUTED HDL; DRUG-DELIVERY; GENE DELIVERY; FOAM CELL; ATHEROSCLEROSIS; THERAPY; SIRNA; NANOSTRUCTURES;
D O I：
10.1021/acs.biomac.7b00436
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
A biofunctional polymer lipid hybrid high density lipoprotein-mimicking nanoparticle (HNP) loading anti-miR155 was constructed for combined antiatherogenic effects on macrophages. The HNP consisted of an anti-miR155 core condensed by acid-labile polyethylenimine (acid labile PEI) polymers and a lipid bilayer coat that was decorated with apolipoprotein A-1, termed acid-labile PEI/HNP. The acid-labile PEI was synthesized with low-molecular-weight PEI and glutaraldehyde to reduce the cytotoxicity and facilitate nucleic acids escaping from acidic endolysosomes. The increased silencing efficiency of acid-labile PEI/HNP was ascribed to the clathrin-mediated endocytosis endolysosomal escape. Decreased intracellular reactive oxygen species production and DiI-oxLDL uptake revealed the antioxidant activities of both anti-miR155 and HNP. Cholesterol efflux assay indicated the potential of HNP in reverse cholesterol transport. Collectively, the acid-labile PEI/HNP not only realized the efficacy of anti-miR155 in macrophages but also exerted the antiatherosclerotic biofunction of HNP.
引用
收藏
页码：2286 / 2295
页数：10
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