Membrane‐Targeted Nanoparticles for Neuronal Photomodulation

Selective targeting of nanoparticles to the neuronal interface is central for the tailored development of precision neurotechnologies. Here, we report the targeting of gold bipyramids, as a model nanomaterial, on the membrane of primary neurons using a bioorthogonal approach. In a two-step process, linker molecules anchor to receptors that expose trans-cyclooctene, which forms a covalent bond with the tetrazine functional group on nanoparticles, leading to the retention of hundreds of nanoparticles per cell. Selective labeling of neuronal membranes with plasmonic nanoparticles via a bioorthogonal strategy enabled inhibition of neuronal activity through photothermal effects under NIR laser irradiation in synchronized cell cultures. The linker and/or nanoparticles alone have a negligible effect on neuromodulation. Nanoparticle retention at the membrane is rapid, requiring only one hour of total incubation, with no cytotoxic effect. These results expand the repertoire of light-activated nanomaterials for non-invasive neuromodulation.