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

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.