Modular poly(ethylene glycol) ligands for biocompatible semiconductor and gold nanocrystals with extended pH and ionic stability

Abstract

We describe the design of new ligands made by coupling commercially available poly(ethylene glycol) methyl ether (mPEG, HO-PEG-OCH3) and thioctic acid (TA) via a stable amide bond to form TA-PEG-OCH3 molecules. The ligands were obtained by a simple transformation of the hydroxyl group on the mPEG into an amine group, followed by attachment of TA viaN,N′-dicyclohexylcarbodiimide (DCC) coupling. Following ring opening of the 1,2-dithiolane on the TA-PEG-OCH3 to form a dihydrolipoic acid (DHLA) group, DHLA-PEG-OCH3 was obtained. Cap exchange of nanoparticles with DHLA-PEG-OCH3 provided dispersions in buffer solutions that were stable over a broad pH range (from 3 to 13 for CdSe-ZnS QDs and 2–13 for Au nanoparticles). Using DHLA-PEG-OCH3 either neat or mixed with amine- or carboxyl-terminated ligands (DHLA-PEG-NH2 or DHLA-PEG-COOH) allowed tuning of the surface functionalities of these nanoparticles. Microinjection of the ligand-exchanged QDs into live cells indicated that the newly capped QDs were stable and well dispersed in the cell cytosol for up to 32 h following delivery. The fluorescence distribution and its evolution over time of these DHLA-PEG-OCH3-QDs indicate improved intracellular stability and reduced non-specific interactions compared to nanocrystals capped with DHLA-PEG-OH.