Macrophage biomimetic nanoparticle-targeted functional extracellular vesicle micro-RNAs revealed via multiomics analysis alleviate sepsis-induced acute lung injury

被引：14

作者：

Wang, Guozhen ^{[1
,2
,3
,4
]}

Ma, Xiaoxin ^{[3
,4
]}

Huang, Weichang ^{[1
,2
]}

Wang, Shuanghu ^{[5
]}

Lou, Anni ^{[1
]}

Wang, Jun ^{[2
,6
]}

Tu, Yingfeng ^{[7
]}

Cui, Wanfu ^{[1
]}

Zhou, Wangmei ^{[1
]}

Zhang, Wenyong ^{[1
]}

Li, Yue ^{[8
]}

Geng, Shiyu ^{[1
,2
]}

Meng, Ying ^{[9
]}

Li, Xu ^{[1
,2
]}

机构：

[1] Southern Med Univ, Nanfang Hosp, Dept Emergency Med, Guangzhou 510515, Peoples R China

[2] Southern Med Univ, State Key Lab Organ Failure Res, Guangdong Prov Key Lab Viral Hepatitis Res, Guangzhou 510515, Guangdong, Peoples R China

[3] Jinan Univ, Shenzhen Peoples Hosp, Dept Gastroenterol, Clin Med Coll 2, Shenzhen 518020, Guangdong, Peoples R China

[4] Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China

[5] Wenzhou Med Univ, Lishui Peoples Hosp, Cent Lab, Lishui Hosp, Lishui 323000, Zhejiang, Peoples R China

[6] Southern Med Univ, Nanfang Hosp, Dept Gastroenterol, Guangdong Prov Key Lab Gastroenterol, Guangzhou 510515, Guangdong, Peoples R China

[7] Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Peoples R China

[8] Southern Med Univ, Gen Hosp Southern Theatre Command, Dept Intens Care Unit, Guangzhou 510515, Peoples R China

[9] Southern Med Univ, Nanfang Hosp, Dept Resp Dis, Guangzhou 510515, Peoples R China

来源：

JOURNAL OF NANOBIOTECHNOLOGY | 2024年 / 22卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Sepsis; Acute lung injury; Extracellular vesicles; Single-cell RNA sequencing; Macrophage membrane nanoparticles; RESPIRATORY-DISTRESS-SYNDROME; OXIDATIVE STRESS; BLOOD; CLEARANCE;

D O I：

10.1186/s12951-024-02597-z

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 090105 [作物生产系统与生态工程];

摘要：

Patients who suffer from sepsis typically experience acute lung injury (ALI). Extracellular vesicles (EVs) contain miRNAs, which are potentially involved in ALI. However, strategies to screen more effective EV-miRNAs as therapeutic targets are yet to be elucidated. In this study, functional EV-miRNAs were identified based on multiomics analysis of single-cell RNA sequencing of targeted organs and serum EV (sEV) miRNA profiles in patients with sepsis. The proportions of neutrophils and macrophages were increased significantly in the lungs of mice receiving sEVs from patients with sepsis compared with healthy controls. Macrophages released more EVs than neutrophils. MiR-125a-5p delivery by sEVs to lung macrophages inhibited Tnfaip3, while miR-221-3p delivery to lung neutrophils inhibited Fos. Macrophage membrane nanoparticles (MM NPs) loaded with an miR-125a-5p inhibitor or miR-221-3p mimic attenuated the response to lipopolysaccharide (LPS)-induced ALI. Transcriptome profiling revealed that EVs derived from LPS-stimulated bone marrow-derived macrophages (BMDMs) induced oxidative stress in neutrophils. Blocking toll-like receptor, CXCR2, or TNF alpha signaling in neutrophils attenuated the oxidative stress induced by LPS-stimulated BMDM-EVs. This study presents a novel method to screen functional EV-miRNAs and highlights the pivotal role of macrophage-derived EVs in ALI. MM NPs, as delivery systems of key sEV-miRNA mimics or inhibitors, alleviated cellular responses observed in sepsis-induced ALI. This strategy can be used to reduce septic organ damage, particularly lung damage, by targeting EVs.

引用

页数：21

共 51 条

[1]

Toll-like receptors in the induction of the innate immune response [J].