Multivalent binding between membrane receptors and nanoconstructs—nanoparticle (NP) cores surrounded by ligand shells—is important for targeted delivery of NPs and enhanced cellular uptake. Besides molecular multivalency (multiple presenting surface ligands), structural multivalency (multiple curvatures) of anisotropic NPs plays a key role in increasing NP specificity to receptors compared to spherical particles. Au nanostars (AuNS) have been used as biocompatible nanoprobes for label-free single-particle tracking; however, how their geometry affects NP-cell interactions is not well established. In this work, we used differential interference contrast (DIC) microscopy to probe single-nanoconstruct dynamics of functionalized AuNS that have similar densities of receptor-targeting ligands but different structural anisotropy. Nanoconstructs with longer and fewer branches showed more restricted rotation compared to ones with shorter and more branches on cell membranes expressing the targeted human epidermal growth factor receptor 2 (HER2). More confined rotation was attributed to the higher targeting efficiency towards HER2, confirmed by the lower uptake under inhibition of clathrin-mediated endocytosis—the major endocytosis pathway of ligand-bound HER2. These results show that detailed structural anisotropy is crucial in determining the cell-nanoconstruct interactions.

Structure-dependent dynamics of targeting nanoconstructs on live-cell membranes

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.