3 years ago

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

Biofunctional Polymer–Lipid Hybrid High-Density Lipoprotein-Mimicking Nanoparticles Loading Anti-miR155 for Combined Antiatherogenic Effects on Macrophages
Xiaoju Zhou, Yi Zhao, Jianping Liu, Jian Hua He, Cuiping Jiang, Yun Yang, Zitong Qi, Jing Lu, Wenli Zhang
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 and successful 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.

Publisher URL: http://dx.doi.org/10.1021/acs.biomac.7b00436

DOI: 10.1021/acs.biomac.7b00436

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