The dual-function of lipoic acid groups as surface anchors and sulfhydryl reactive sites on polymer-stabilized QDs and Au nanocolloids.

Abstract

Coating inorganic nanocrystals [e.g., quantum dots (QDs) and gold nanoparticles] with polymer ligands presenting multiple lipoic acid anchoring groups provides nanocolloids with remarkable long-term colloidal and photophysical stability. Here, we show that the natural swelling of macromolecules leaves a fraction of the lipoic acid groups in the surface coating free, which are targeted for activation and conjugation to target molecules, using the reliable sulfhydryl-to-maleimide reaction. This implies that simple and efficient functionalization of the nanocrystals can be achieved without introducing additional reactive groups in the coating. We apply a photomediated ligand exchange strategy to luminescent QDs and AuNPs and react the resulting nanocrystals with maleimide Cy3 dye. We then use optical absorption and resonance energy transfer measurements applied to QD-Cy3 and AuNP-Cy3 conjugates to extract estimates for the fraction of accessible lipoic acid groups per QD or AuNP. In addition, we demonstrate the potential utility of this approach by constructing a ratiometric pH sensor made of QD-SNARF conjugates. Our ligand design combined with the photoligation strategy yield colloidally stable dispersions of QDs and AuNPs that present accessible reactive thiols, without introducing new functionalities or requiring disulfide reducing reagents, making them useful for potential use in applications such as biological sensing and imaging.