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 5AC (MUC5AC) 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.

中文翻译：

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用于哮喘治疗的铁蛋白 H 链蛋白纳米颗粒表面显示的抗 EGFR 单链 Fv 抗体片段

表皮生长因子受体 (EGFR) 依赖性信号传导有助于哮喘的病理生理学。然而，这些发现尚未转化为临床应用。我们最近生成了基于铁蛋白 H 链蛋白 (FTH1) 的纳米颗粒，在 FTH1 表面具有抗 EGFR 单链 Fv (anti-EGFR scFv)，即抗 EGFR scFv-FTH1/FTH1 纳米颗粒。在本研究中，我们发现这些纳米颗粒可以特异性结合 EGFR 表达细胞，导致 EGFR 和粘蛋白 5AC (MUC5AC) 蛋白表达的下调和屋尘螨 (HDM) 刺激的人支气管上皮 16HBE 和脂多糖的生长抑制(脂多糖)-激活的鼠类巨噬细胞样 RAW264.7 细胞。在体内，腹腔内给予抗 EGFR scFv-FTH1/FTH1 纳米颗粒（而非 FTH1 纳米颗粒）可缓解主要病理症状，包括气道高反应性、气道炎症、杯状细胞增生、粘液过度产生和过敏原卵白蛋白中 Th2 细胞因子的释放增加(OVA) 诱导的哮喘小鼠模型。重要的是，在给药期间，这些纳米颗粒对健康和哮喘小鼠都是安全的，并且在控制气道炎症方面比 EGFR 单克隆抗体西妥昔单抗更有效。总之，我们的研究为通过靶向 EGFR 控制气道炎症治疗哮喘提供了见解。类似的策略可用于制造基于 scFv 的重组蛋白纳米颗粒，用于其他临床应用。