To explore the potential for use of ligand-conjugated nanocrystals to target cell surface receptors, ion channels, and transporters, we explored the ability of serotonin-labeled CdSe nanocrystals (SNACs) to interact with antidepressant-sensitive, human and Drosophila serotonin transporters (hSERT, dSERT) expressed in HeLa and HEK-293 cells. Unlike unconjugated nanocrystals, SNACs were found to dose-dependently inhibit transport of radiolabeled serotonin by hSERT and dSERT, with an estimated half-maximal activity (EC50) of 33 (dSERT) and 99 μM (hSERT). When serotonin was conjugated to the nanocrystal through a linker arm (LSNACs), the EC50 for hSERT was determined to be 115 μM. Electrophysiology measurements indicated that LSNACs did not elicit currents from the serotonin-3 (5HT3) receptor but did produce currents when exposed to the transporter, which are similar to those elicited by antagonists. Moreover, fluorescent LSNACs were found to label SERT-transfected cells but did not label either nontransfected cells or transfected cells coincubated with the high-affinity SERT antagonist paroxetine. These findings support further consideration of ligand-conjugated nanocrystals as versatile probes of membrane proteins in living cells.
CITATION STYLE
Rosenthal, S. J., Tomlinson, I., Adkins, E. M., Schroeter, S., Adams, S., Swafford, L., … Blakely, R. D. (2002). Targeting cell surface receptors with ligand-conjugated nanocrystals. Journal of the American Chemical Society, 124(17), 4586–4594. https://doi.org/10.1021/ja003486s
Mendeley helps you to discover research relevant for your work.