Prominent Enhancement of Peptide-Mediated Targeting Efficiency for Human Hepatocellular Carcinomas with Composition-Engineered Protein Corona on Gold Nanoparticles

We examined the feasibility of optimizing protein corona composition to improve the targeting efficiency of a tumor targeting peptide (Pep2) functionalized AuNPs (Au-Pep2) by coupling zwitterionic peptide (EK) and stearine (fat) separately or simultaneously. In vitro results demonstrated that Au-Pep2-EK and Au-Pep2-EK-fat exhibited higher binding affinity towards tumor cells than Au-Pep2 in fetal bovine serum (FBS)-and mouse serum (MS)-containing medium. Such enhancement could be considered as a result of the anti-fouling peptide EK that can create a hydration layer to resist nonspecific protein adsorption, as well as fat modification for specific albumin binding. In vivo results further revealed that, at 24 h post i.v. injection, such engineering optimal Au-Pep2-EK-fat achieved nearly 10-fold and 2-fold greater tumor accumulation than Au-Pep2 and Au-Pep2-EK, respectively, which may attributed to the prolonged blood clearance half-life as a result of pre-albumin coating. This work suggests nanoparticle surface chemistry as a readily tunable parameter in future rational exploiting of protein corona, and provides a feasible strategy for improving the targeting efficiency of ligand-modified nanoparticles.