文献类型：期刊文献

英文题名：Anti-EGFR Single-Chain Fv Antibody Fragment Displayed on the Surface of Ferritin H-Chain Protein Nanoparticle for Asthma Therapy

作者：Zhang, Tianbao[1];Wang, Rongrong[1];Li, Zihui[1];Wang, Liang[1];Gao, Zonglin[1];Tu, Yaping[2];Cao, Xuni[1]

机构：[1]East China Univ Sci & Technol, Sch Biotechnol, Shanghai 200237, Peoples R China;[2]Creighton Univ, Sch Med, Dept Pharmacol & Neurosci, Omaha, NE 68178 USA

年份：2021

卷号：4

期号：9

起止页码：6690

外文期刊名：ACS APPLIED BIO MATERIALS

收录：EI(收录号：20214211023691);WOS:【ESCI(收录号:WOS:000699828900010)】；

基金：This work was supported by the National Natural Science Foundation of China (Grant No. 21375039), Shanghai Committee of Science and Technology (Grant No. 19142201300, 18142202600), the Research Program of Shanghai Chemical Reagent Research Institute Co., Ltd. (Grant No. F100-81707, F100-81903).

语种：英文

外文关键词：ferritin H-chain; epidermal growth factor receptor; nanoparticles; single-chain antibody; asthma

摘要：Epidermal growth factor receptor (EGFR)-dependent signaling contributes to the pathophysiology of asthma. However, these findings have not been translated into a clinical application. We recently generated ferritin H-chain protein (FTH1)-based nanoparticles with an anti-EGFR single-chain Fv (anti-EGFR scFv) on the surface of FTH1, namely, anti-EGFR scFv-FTH1/FTH1 nanoparticles. In the present study, we found that these nanoparticles could specifically bind to EGFR-expressing cells, leading to downregulation of EGFR and mucin SAC (MUCSAC) protein expression and growth suppression of House Dust Mite (HDM)-stimulated human bronchial epithelial 16HBE and lipopolysaccharides (LPS)-activated murine macrophage-like RAW264.7 cells. In vivo, intraperitoneal administration of anti-EGFR scFv-FTH1/FTH1 nanoparticles, but not FTH1 nanoparticles, alleviated the major pathological symptoms including airway hyperresponsiveness, airway inflammation, goblet cell hyperplasia, mucus hyperproduction, and increased release of Th2 cytokines in an allergen ovalbumin (OVA)-induced asthma mouse model. Importantly, during the dosing period these nanoparticles were safe for both heathy and asthmatic mice, and more effective in controlling airway inflammation than cetuximab, an EGFR monoclonal antibody. Altogether, our studies provide insights into the control of airway inflammation for treatment of asthma by targeting EGFR. The similar strategy can be used to fabricate scFv-based recombinant protein nanoparticles for other clinical applications.