title: Multifunctional compact zwitterionic ligands for preparing robust biocompatible semiconductor quantum dots and gold nanoparticles.
abstract: We describe the synthesis of a series of four different ligands which are used to prepare hydrophilic, biocompatible luminescent quantum dots (QDs) and gold nanoparticles (AuNPs). Overall, the ligands are designed to be compact while still imparting a zwitterionic character to the NPs. Ligands are synthesized appended to a bidentate dihydrolipoic acid- (DHLA) anchor group, allowing for high-affinity NP attachment, and simultaneously incorporate tertiary amines along with carboxyl and/or hydroxyl groups. These are placed in close proximity within the ligand structure and their capacity for joint ionization imparts the requisite zwitterionic nature to the nanocrystal. QDs functionalized with the four different compact ligands were subjected to extensive physical characterization including surface charge, wettability, hydrodynamic size, and tolerance to a wide pH range or high salt concentration over time. The utility of the compact ligand coated QDs was further examined by testing of direct conjugation to polyhistidine-appended protein and peptides, aqueous covalent-coupling chemistry, and the ability to engage in Förster resonance energy transfer (FRET). Conjugating cell penetrating peptides to the compact ligand coated QD series facilitated their rapid and efficient cellular uptake, while subsequent cytotoxicity tests showed no apparent decreases in cell viability. In vivo biocompatibility was also demonstrated by microinjecting the compact ligand coated QDs into cells and monitoring their stability over time. Inherent benefits of the ligand design could be extended beyond QDs as AuNPs functionalized with the same compact ligand series showed similar colloidal properties. The strong potential of these ligands to expand NP capabilities in many biological applications is highlighted.
authors: Optical Sciences Division, Code 5611, U.S. Naval Research Laboratory, Washington, D.C. 20375, USA. susumu@ccs.nrl.navy.mil
authors: Kimihiro
authors: K
authors: Susumu
authors: Eunkeu
authors: E
authors: Oh
authors: James B
authors: JB
authors: Delehanty
authors: Juan B
authors: JB
authors: Blanco-Canosa
authors: Brandy J
authors: BJ
authors: Johnson
authors: Vaibhav
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authors: Jain
authors: William Judson
authors: WJ
authors: Hervey
authors: W Russ
authors: WR
authors: Algar
authors: Kelly
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authors: Boeneman
authors: Philip E
authors: PE
authors: Dawson
authors: Igor L
authors: IL
authors: Medintz