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Combined Delivery of angiopoietin-1 Gene and Simvastatin Mediated by Anti-Intercellular Adhesion molecule-1 Antibody-Conjugated Ternary Nanoparticles for Acute Lung Injury Therapy

Saiping Jiang, Shujuan Li, Jingbo Hu, Xiaoling Xu, Xiaojuan Wang, Xuqi Kang, Jing Qi, Xiaoyang Lu, Jiahui Wu, Yongzhong Du, Yonghong Xiao

Nanomedicine. 2019 Jan;15(1):25-36.

PMID: 30193816

Abstract:

Effective treatment for acute lung injury (ALI) is in high demand. Lung-targeted ternary nanoparticles containing anti-intercellular adhesion molecule-1 (ICAM-1) antibody-conjugated simvastatin-loaded nanostructured lipid carrier (ICAM/NLC), protamine (Pro), and angiopoietin-1 (Ang-1) gene (ICAM-NLC/Pro/Ang) were developed for ALI therapy. The ternary nanoparticles with different weight ratios of ICAM-NLC to Ang-1 gene were prepared via charge interaction. The anti-ICAM-1 antibody-conjugated ternary nanoparticles exhibited higher cellular uptake and transfection efficiency (from 26.7% to 30.9%) in human vascular endothelial cell line EAhy926 than the non-targeted control. The largest size of ICAM-NLC/Pro/Ang (357.1 nm) was employed for further study, which significantly up-regulated in vitro and in vivo Ang-1 protein expression. In vivo i.v. administration of ICAM-NLC/Pro/Ang (357.1 nm) significantly attenuated pulmonary TNF-α and IL-6 levels, inflammatory cell infiltration, and led to positive histological improvements in lipopolysaccharide-induced ALI mice. Collectively, the ICAM-NLC/Pro/Ang that co-delivered simvastatin and Ang-1 gene may represent a potential treatment modality for ALI.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR4248741 Angiopoietin-1 human Angiopoietin-1 human Price
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