An integrated "Engage & Evasion" approach for mononuclear phagocyte system escape and efficient extracellular vesicle therapy

被引：0

作者：

Liu, Hongman ^{[1
,2
,3
,4
]}

Li, Mengting ^{[1
,2
]}

Xiang, Bing ^{[4
]}

Yang, Ziying ^{[1
,2
]}

Cao, Shiyu ^{[1
,2
]}

Gong, Wen ^{[4
]}

Li, Jingjing ^{[1
,2
]}

Zhou, Wenjing ^{[6
,7
]}

Ding, Liang ^{[1
,2
]}

Tang, Qingsong ^{[1
,2
]}

Wang, Shengnan ^{[1
,2
]}

Tang, Jin ^{[5
]}

Fan, Zixuan ^{[5
]}

He, Ke ^{[5
]}

Jiang, Xuan ^{[5
]}

Shen, Zhenya ^{[1
,2
]}

Chen, Weiqian ^{[1
,2
]}

Hui, Jie ^{[1
,2
,3
]}

机构：

[1] Soochow Univ, Affiliated Hosp 1, Suzhou Med Coll, Dept Cardiovasc Surg, Suzhou, Peoples R China

[2] Soochow Univ, Inst Cardiovasc Sci, Suzhou Med Coll, Suzhou, Peoples R China

[3] Soochow Univ, Affiliated Hosp 1, Dept Cardiol, Suzhou, Peoples R China

[4] Qingdao Univ, Affiliated Taian City Cent Hosp, Dept Cardiovasc Med, Tai An, Peoples R China

[5] Sun Yat Sen Univ, Sch Med, Shenzhen Key Lab Syst Med Inflammatory Dis, Shenzhen, Peoples R China

[6] Tianjin Univ, Fac Med, Sch Life Sci, Tianjin, Peoples R China

[7] Chinese Acad Sci, Hangzhou Inst Med HIM, Hangzhou, 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; 国家重点研发计划;

关键词：

Ischemic disease; Extracellular vesicle; Mononuclear phagocyte system; CD47; Phagocytosis; ACTIVATION; DELIVERY;

D O I：

10.1186/s12951-024-03032-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 ; 0836 ; 090102 ; 100705 ;

摘要：

Ischemic diseases are major contributors to global morbidity and mortality, posing a substantial threat to human health. Extracellular vesicles (EVs) play an essential role in enhancing neovascularization in ischemic tissues, thereby facilitating tissue repair and regeneration. However, the utilization of EVs is hindered by their rapid uptake and clearance by the mononuclear phagocyte system (MPS), which markedly impedes their therapeutic efficacy and organ-specific accumulation. Notably, CD47, upon binding to signal regulatory protein alpha, initiates a "don't eat me" signal, enabling immune evasion from the MPS. Our research has demonstrated that phagocytes predominantly engulf CD47low dendritic DC2.4 cell-derived EVs (DV), while engineered CD47high EVs (MV47) experience minimal ingestion. Leveraging these findings, we have developed a dual-faceted "Engage & Evasion" strategy. Initially, DVs were employed to saturate the MPS, serving as the "engage" component. Subsequently, MV47, fortified with CD47, was introduced for "evasion" purposes. This approach effectively minimized entrapment by the liver and spleen, boosted serum concentration, and enhanced final accumulation in non-MPS organs. In summary, our "Engage & Evasion" therapeutic strategy offers a promising avenue to enhance EV therapeutic potential against ischemic challenges through improved systemic distribution.

引用

页数：15