Small and Stable Sulfobetaine Zwitterionic Quantum Dots for Functional Live-Cell Imaging

We have developed a novel surface coating for semiconductor quantum dots (QDs) based on a heterobifunctional ligand that overcomes most of the previous limits of these fluorescent probes in bioimaging applications. Here we show that QDs capped with bidentate zwitterionic dihydrolipoic acid-sulfobetaine (DHLA-SB) ligands are a favorable alternative to polyethylene glycol-coated nanoparticles since they combine small sizes, low nonspecific adsorption, preserved optical properties, and excellent stability over time and a wide range of pH and salinity. Additionally, these QDs can easily be functionalized with biomolecules such as streptavidin (SA) and biotin. We applied streptavidin-functionalized DHLA-SB QDs to track the intracellular recycling of cannabinoid receptor 1 (CB1R) in live cells. These QDs selectively recognized the pool of receptors at the cell surface via SA-biotin interactions with negligible nonspecific adsorption. The QDs retained their optical properties, allowing the internalization of CB1R into endosomes to be followed. Moreover, the cellular activity was apparently unaffected by the probe.