Pulmonary delivery of cell membrane-derived nanovesicles carrying anti-miRNA155 oligonucleotides ameliorates LPS-induced acute lung injury

寡核苷酸 细胞 化学 肺损伤 药理学 医学 生物化学 内科学 基因 肺纤维化
作者
Chuanyu Zhuang,Minji Kang,Jihun Oh,Minhyung Lee
出处
期刊:Regenerative Biomaterials [University of Oxford]
卷期号:11
标识
DOI:10.1093/rb/rbae092
摘要

Abstract Acute lung injury (ALI) is a devastating inflammatory disease. MicroRNA155 (miR155) in alveolar macrophages and lung epithelial cells enhances inflammatory reactions by inhibiting the suppressor of cytokine signaling 1 (SOCS1) in ALI. Anti-miR155 oligonucleotide (AMO155) have been suggested as a potential therapeutic reagent for ALI. However, a safe and efficient carrier is required for delivery of AMO155 into the lungs for ALI therapy. In this study, cell membrane-derived nanovesicles (CMNVs) were produced from cell membranes of LA4 mouse lung epithelial cells and evaluated as a carrier of AMO155 into the lungs. For preparation of CMNVs, cell membranes were isolated from LA4 cells and CMNVs were produced by extrusion. Cholesterol-conjugated AMO155 (AMO155c) was loaded into CMNVs and extracellular vesicles (EVs) by sonication. The physical characterization indicated that CMNVs with AMO155c (AMO155c/CMNV) were membrane-structured vesicles with a size of ∼120 nm. The delivery efficiency and therapeutic efficacy of CMNVs were compared with those of EVs or polyethylenimine (25 kDa, PEI25k). The delivery efficiency of AMO155c by CMNVs was similar to that by EVs. As a result, the miR155 levels were reduced by AMO155c/CMNV and AMO155c/EV. AMO155c/CMNV were administered intratracheally into the ALI models. The SOCS1 levels were increased more efficiently by AMO155c/CMNV than by the others, suggesting that miR155 effectively was inhibited by AMO155c/CMNV. In addition, the inflammatory cytokines were reduced more effectively by AMO155c/CMNV than they were by AMO155c/EV and AMO155c/PEI25k, reducing inflammation reactions. The results suggest that CMNVs are a useful carrier of AMO155c in the treatment of ALI.
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