High-Curvature Features on Branched Nanoconstructs Circumvent Protein Corona Interference

This paper reports how the local nanoscale curvature on nanoparticle constructs determines the protein corona distribution in biological conditions. Using transmission electron microscopy, we found that DNA-gold nanostar nanoconstructs (DNA-AuNS) having positive-curvature tips <5 nm in radius showed less dense and less uniform protein corona layers compared to 50 nm gold nanospheres (DNA-50NPs). Statistical analysis based on type of curvature on AuNS revealed that the protein layer thickness on the tips was lower than that on the neutral and negative curvature regions. Since protein coronas screen ligands on nanoparticles, we used DNA hybridization to evaluate whether local ligand functionality was preserved after adsorption of proteins. DNA-AuNS nanoconstructs with less dense protein coronas hybridized more 5 nm gold nanosphere probes (5NPs) compared to DNA-50NPs. Without the protein corona layer, the two classes of nanoconstructs hybridized higher numbers of 5NPs, and differences due to NP shape were minimal. Notably, we found that the tips of DNA-AuNS nanoconstructs exhibited higher percentages of hybridization compared to neutral and negative curvature regions; this trend was independent of DNA sequence. Our work demonstrates the importance of nanoconstruct curvature in mitigating local protein adsorption and preserving ligand functionality at the single-particle level.