Nanoparticle (NP) shape plays a key role in protein corona formation and targeted drug delivery. Although NP branch length can influence the composition of proteins that adsorb to NP, how branch length affects binding efficacy between grafted ligands and cell-membrane receptors is unknown. Using live-cell, single-particle tracking, we found that aptamer-functionalized gold nanostar nanoconstructs with longer branches showed improved binding efficacy to the targeted receptors on cancer cell membranes. We showed that inhibiting NP−receptor binding promoted nonspecific interactions, which increased the rotational speed of long-branched nanoconstructs but did not affect that of short constructs. We attribute the higher binding efficacy of long-branched nanoconstructs to a lower protein adsorption at the tips which facilitate binding of aptamers to targeted receptors. Our study reveals the significance of nanoparticle branch length in regulating local chemical environment and interactions with live cells at the single-particle level.
