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

页码：2286 / 2295

页数：10

共 52 条

[51] Plaque-hyaluronidase-responsive high-density-lipoprotein-mimetic nanoparticles for multistage intimal-macrophage-targeted drug delivery and enhanced anti-atherosclerotic therapy
Zhang, Mengyuan
He, Jianhua
Jiang, Cuiping
Zhang, Wenli
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Liu, Jianping
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Corbin, Ian
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Zheng, Gang
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