Targeting Ability of Affibody-Functionalized Particles Is Enhanced by Albumin but Inhibited by Serum Coronas

Protein coronas formed on engineered particles can alter their targeting ability as they enter biological environments. Here, we engineer polymer-coated silica particles and investigate the influence of protein coronas derived from various sources. The particles were functionalized with a small antibody-mimetic ligand (affibody), and their targeting ability to cancer cells in the presence of protein coronas was determined. Protein coronas derived from human serum showed a dramatic inhibition of specific particle-cell association (from ∼70 to ∼7%), whereas the most abundant protein in human serum-human serum albumin-enhanced the specific association of functionalized particles to SK-OV-3 human ovary cancer cells (to ∼90%). This study shows how protein coronas can both facilitate and impede targeting and provides key insights into the importance of challenging engineered particles with multicomponent biologically relevant environments.