Resolving Single-Nanoconstruct Dynamics during Targeting and Nontargeting Live-Cell Membrane Interactions

This paper describes how differences in the dynamics of targeting and nontargeting constructs can provide information on nanoparticle (NP)–cell interactions. We probed translational and rotational dynamics of functionalized Au nanostar (AuNS) nanoconstructs interacting with cells in serum-containing medium. We found that AuNS with targeting ligands had a larger dynamical footprint and faster rotational speed on cell membranes expressing human epidermal growth factor receptor 2 (HER-2) receptors compared to that of AuNS with nontargeting ligands. Targeting and nontargeting nanoconstructs displayed distinct membrane dynamics despite their similar protein adsorption profiles, which suggests that targeted interactions are preserved even in the presence of a protein corona. The high sensitivity of single-NP dynamics can be used to compare different nanoconstruct properties (such as NP size, shape, and surface chemistry) to improve their design as delivery vehicles.