通过肺部输送携带抗miRNA155寡核苷酸的细胞膜衍生纳米颗粒可改善LPS诱导的急性肺损伤。

IF 5.6 1区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS
Regenerative Biomaterials Pub Date : 2024-08-16 eCollection Date: 2024-01-01 DOI:10.1093/rb/rbae092
Chuanyu Zhuang, Minji Kang, Jihun Oh, Minhyung Lee
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引用次数: 0

摘要

急性肺损伤(ALI)是一种破坏性炎症疾病。肺泡巨噬细胞和肺上皮细胞中的微RNA155(miR155)会抑制细胞因子信号转导抑制因子1(SOCS1),从而增强ALI的炎症反应。抗 miR155 寡核苷酸(AMO155)被认为是治疗 ALI 的潜在试剂。然而,将 AMO155 运送到肺部治疗 ALI 需要一种安全高效的载体。本研究利用 LA4 小鼠肺上皮细胞的细胞膜制备了细胞膜衍生纳米颗粒(CMNVs),并对其作为将 AMO155 送入肺部的载体进行了评估。在制备 CMNVs 时,从 LA4 细胞中分离出细胞膜,并通过挤压法制备 CMNVs。通过超声将胆固醇结合的AMO155(AMO155c)载入CMNVs和细胞外囊泡(EVs)。物理表征表明,含有 AMO155c 的 CMNV(AMO155c/CMNV)为膜结构囊泡,大小为 120 nm。研究人员比较了 CMNV 与 EV 或聚乙烯亚胺(25 kDa,PEI25k)的递送效率和疗效。CMNVs传递AMO155c的效率与EVs相似。因此,AMO155c/CMNV 和 AMO155c/EV 降低了 miR155 的水平。给 ALI 模型气管内注射 AMO155c/CMNV。与其他药物相比,AMO155c/CMNV 更有效地提高了 SOCS1 的水平,这表明 AMO155c/CMNV 有效地抑制了 miR155。此外,与 AMO155c/EV 和 AMO155c/PEI25k 相比,AMO155c/CMNV 能更有效地减少炎症细胞因子,从而减轻炎症反应。结果表明,CMNV 是 AMO155c 治疗 ALI 的有效载体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pulmonary delivery of cell membrane-derived nanovesicles carrying anti-miRNA155 oligonucleotides ameliorates LPS-induced acute lung injury.

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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来源期刊
Regenerative Biomaterials
Regenerative Biomaterials Materials Science-Biomaterials
CiteScore
7.90
自引率
16.40%
发文量
92
审稿时长
10 weeks
期刊介绍: Regenerative Biomaterials is an international, interdisciplinary, peer-reviewed journal publishing the latest advances in biomaterials and regenerative medicine. The journal provides a forum for the publication of original research papers, reviews, clinical case reports, and commentaries on the topics relevant to the development of advanced regenerative biomaterials concerning novel regenerative technologies and therapeutic approaches for the regeneration and repair of damaged tissues and organs. The interactions of biomaterials with cells and tissue, especially with stem cells, will be of particular focus.
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