EGFR Affibody and PEG functionalized protein nanoparticles: Sustaining targeting and macrophage evasion.

When nanoparticles are introduced into a biological environment, serum proteins rapidly attach to their surfaces, leading to opsonization and subsequent rapid clearance by the immune system. In this study, we functionalized protein nanoparticles with PEG to impart stealth properties, aiming to reduce immune recognition. By incorporating EGFRAfb, we conferred targeting capabilities to the PEGylated protein nanoparticles, demonstrating their ability to specifically bind to target cells even after PEGylation. Additionally, the stealth effect conferred by PEGylation effectively prevented phagocytosis by macrophages. Taken together, these results indicate that PEGylated protein nanoparticles not only exhibit increased in vivo half-life due to reduced opsonization but also maintain cell-specific targeting capabilities.