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基于凋亡小体的仿生杂交纳米囊泡减轻细胞因子风暴用于脓毒症治疗

Apoptotic body based biomimetic hybrid nanovesicles to attenuate cytokine storms for sepsis treatment.

作者信息

Lan Hongbing, Zhou Zhanhao, Hu Qian, Xie Qi, Li Xiaonan, Tian Tianyi, Wang Yi, Yang Conglian, Kong Li, Fu Dehao, Guo Yuanyuan, Zhang Zhiping

机构信息

Department of Pharmacy, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, 541002, China.

Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, 430030, China.

出版信息

J Nanobiotechnology. 2024 Dec 19;22(1):775. doi: 10.1186/s12951-024-03058-3.

DOI:10.1186/s12951-024-03058-3
PMID:39695736
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11656764/
Abstract

Sepsis is a severe immune response to pathogens that is associated with high mortality rate and a paucity of efficacious treatment options. It is characterized by the hyperactivation of macrophages and the occurrence of cytokine storms. Given the anti-inflammatory properties of M2 macrophages and their derived apoptotic bodies (AB), as well as the specific uptake of these by macrophages, a novel approach was employed to combine AB with artificial liposomes to create apoptotic body based biomimetic hybrid nanovesicles (L-AB). The L-AB effectively inherited "eat me" signaling molecules on the surface of the AB, thereby facilitating their targeted uptake by macrophages in both in vitro and in vivo settings. The administration of L-AB for the delivery of dexamethasone effectively augmented the therapeutic efficacy of the drug, mitigated macrophage hyperactivation and tissue damage in vivo, and consequently enhanced the survival rate of septic mice. Taken together, these findings suggest that the apoptotic body biomimetic nanovesicles may represent a potential drug delivery system capable of specifically targeting macrophages for the treatment of sepsis.

摘要

脓毒症是对病原体的一种严重免疫反应,与高死亡率和缺乏有效的治疗选择相关。其特征是巨噬细胞的过度活化和细胞因子风暴的发生。鉴于M2巨噬细胞及其衍生的凋亡小体(AB)的抗炎特性,以及巨噬细胞对这些物质的特异性摄取,采用了一种新方法,将AB与人工脂质体结合,以创建基于凋亡小体的仿生杂交纳米囊泡(L-AB)。L-AB有效地继承了AB表面的“吃我”信号分子,从而在体外和体内环境中促进巨噬细胞对其的靶向摄取。给予L-AB用于递送地塞米松有效地增强了药物的治疗效果,减轻了体内巨噬细胞的过度活化和组织损伤,从而提高了脓毒症小鼠的存活率。综上所述,这些发现表明凋亡小体仿生纳米囊泡可能代表一种潜在的药物递送系统,能够特异性靶向巨噬细胞用于治疗脓毒症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a94/11656764/3917a74c83ce/12951_2024_3058_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a94/11656764/4d3dcf62c2fb/12951_2024_3058_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a94/11656764/b8d10562011a/12951_2024_3058_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a94/11656764/61c4945f5b18/12951_2024_3058_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a94/11656764/a8b0f6b172b1/12951_2024_3058_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a94/11656764/a54590e09d06/12951_2024_3058_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a94/11656764/9b350544ef78/12951_2024_3058_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a94/11656764/53ec34a267ca/12951_2024_3058_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a94/11656764/3917a74c83ce/12951_2024_3058_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a94/11656764/4d3dcf62c2fb/12951_2024_3058_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a94/11656764/b8d10562011a/12951_2024_3058_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a94/11656764/61c4945f5b18/12951_2024_3058_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a94/11656764/a8b0f6b172b1/12951_2024_3058_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a94/11656764/a54590e09d06/12951_2024_3058_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a94/11656764/9b350544ef78/12951_2024_3058_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a94/11656764/53ec34a267ca/12951_2024_3058_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a94/11656764/3917a74c83ce/12951_2024_3058_Fig7_HTML.jpg

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本文引用的文献

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Neutrophil ALDH2 is a new therapeutic target for the effective treatment of sepsis-induced ARDS.中性粒细胞 ALDH2 是治疗脓毒症诱导的 ARDS 的一个新的治疗靶点。
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Apoptotic extracellular vesicles restore homeostasis of the articular microenvironment for the treatment of rheumatoid arthritis.
凋亡细胞外囊泡可恢复关节微环境的稳态以治疗类风湿性关节炎。
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Efferocytosis-Inspired Biomimetic Nanoplatform for Targeted Acute Lung Injury Therapy.受胞葬作用启发的用于靶向急性肺损伤治疗的仿生纳米平台。
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Engineered Biomimetic Nanovesicles Based on Neutrophils for Hierarchical Targeting Therapy of Acute Respiratory Distress Syndrome.基于中性粒细胞的工程仿生纳米囊泡用于急性呼吸窘迫综合征的分级靶向治疗。
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