Recent development of dihydrolipoic acid appended ligands for robust and biocompatible quantum dots

Abstract

Biocompatible nanoparticles have recently attracted significant attention due to increasing interest in their use for biological sensing, cellular labeling and in vivo imaging. Semiconductor quantum dots (QDs) with good colloidal stability as well as small hydrodynamic sizes are particularly useful within these applications. We have developed a series of dihydrolipoic acid (DHLA) based surface ligands to enhance the colloidal stability and biocompatibility of water soluble QDs. Modification of DHLA with poly(ethylene glycol) derivatives provided the QDs with extended colloidal stability over a wide pH range and under high salt concentrations, which contrasts with the limited colloidal stability provided by DHLA alone. Functionalization of the PEG termini enabled one to have easy access to the QD surface and construct a variety of stable QD-biomolecules conjugates. A series of DHLA-based compact ligands with zwitterionic character has also been explored to develop compact sized QDs without sacrificing the colloidal stability. Despite their smaller sizes than the PEG analogs, the QDs coated with the zwitterionic ligands still have excellent colloidal stability and minimize nonspecific interactions in biological environments. Recent studies of thiol-based multidentate ligands and ligand exchange methods further improved the colloidal stability and fluorescence quantum yields.