详细信息

anti-EGFR scFv-FTH1/AP1-FTH1纳米粒子的构建及其治疗哮喘小鼠的应用    

Construction of Anti-EGFR scFV-FTH1/AP1-FTH1 Nanoparticles and Its Application in the Treatment of Asthmatic Mice

文献类型:期刊文献

中文题名:anti-EGFR scFv-FTH1/AP1-FTH1纳米粒子的构建及其治疗哮喘小鼠的应用

英文题名:Construction of Anti-EGFR scFV-FTH1/AP1-FTH1 Nanoparticles and Its Application in the Treatment of Asthmatic Mice

作者:汪蓉蓉[1];张天宝[1];曹旭妮[1]

机构:[1]华东理工大学生物工程学院,生物反应器工程国家重点实验室,上海200237

年份:2023

卷号:49

期号:5

起止页码:693

中文期刊名:华东理工大学学报(自然科学版)

外文期刊名:Journal of East China University of Science and Technology

收录:Scopus;北大核心:【北大核心2020】;CSCD:【CSCD_E2023_2024】;

基金:国家自然科学基金(21375039);上海市科委科技创新行动计划资助项目(19142201300)。

语种:中文

中文关键词:哮喘;铁蛋白;纳米粒子;表皮生长因子受体;白介素-4受体

外文关键词:asthma;ferritin H-chain protein;nanoparticles;EGFR;IL-4R

摘要:采用基因工程方法分别将抗表皮生长因子受体(EGFR)的单链抗体(anti-EGFR scFv)和靶向白介素-4-受体(IL-4R)的AP1短肽分别修饰到铁蛋白重链亚基(FTH1)的N端,再通过蛋白表达、体外混合复性后成功制备了anti-EGFR scFv-FTH1/AP1-FTH1双靶向纳米粒子。结果表明:该纳米粒子能正确组装成铁蛋白的特征笼状结构,粒径为(13.2±1.3)nm。在哮喘小鼠模型中发现该纳米粒子能有效抑制哮喘多种症状,且在缓解气道高反应方面的效果优于单靶向anti-EGFR scFv-FTH1/FTH1纳米粒子。
In order to construct ferritin(FTH1)-based dual-functional nanoparticles that actively target both the epidermal growth factor receptor(EGFR)and interleukin-4 receptor(IL-4R),an anti-EGFR single-chain antibody(anti-EGFR scFv)and an IL-4R-targeting AP1 peptide were genetically fused to the N-terminal of FTH1,independently.Then,the anti-EGFR scFv-FTH1/AP1-FTH1 dual-functionalized nanoparticles were prepared by protein expression and in vitro mixed refolding techniques.The results showed that they could be correctly assembled into hollow cage-like nanoparticles with a particle size of(13.2±1.3)nm.In an asthma mouse model,these nanoparticles effectively inhibited inflammatory cell infiltration,goblet cell hyperplasia and mucus secretion.They also showed a reduced airway hyperresponsiveness,and the efficacy was better than that of control nanoparticles,anti-EGFR scFv-FTH1/FTH1,modified with just a single targeting agent.These results provide a new insight into ferritin-based dual-targeted nanoparticles for disease therapy.

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