Zwitterionic lipids when self-assembled around a noble metal nanoparticle can reduce corona formation and keep surface conjugated targeting moieties accessible for interacting with cell surface receptors. We demonstrate in this paper that the unique optical properties of the nanoparticle core facilitate not only a characterization of nanoparticle uptake and binding but also allow for a quantification of the spatial heterogeneity of the targeted cell surface on the single cell level. We show for the example of the epidermal growth factor receptor (EGFR) that the distance-dependent plasmon coupling between nanoparticles targeted to cell surface receptors allow for a reliable quantification of receptor clustering. We validate and benchmark the plasmon coupling approach with fluorescence superresolution fluorescence microscopy. In addition to providing superb optical properties, membrane-wrapped nanoparticles are nanoscale scaffolds that allow for a rational variation of the ligand (in this case epidermal growth factor, EGF) presented on the surface. We took advantage of the nanoparticles’ ability to resolve EGFR clustering and to control the local density of EGF to demonstrate that EGF ligand density and nanoparticle clustering cooperate to achieve a multivalent amplification of EGFR activation. In addition to passivating plasmonic nanoparticle cores, some lipids are by themselves bioactive and can target specific surface receptors. We show in this paper that ganglioside – GM3 – functionalized nanoparticles allow a selective targeting of CD169-expressing myeloid cells (macrophages and dendritic cells) <i>in vitro</i>and <i>in vivo</i>. The GM3-CD169-controlled intracellular fate is further investigated on the single cell level. We demonstrate that the lipid-receptor interactions allow targeting of non-lysosomal compartments that share distinct similarities with virus containing compartments.

Membrane wrapped plasmonic nanoparticles quantify cell surface receptor clustering and reveal lipid-mediated intracellular fates

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

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