Highly Enhanced Affinity of Multidentate versus Bidentate Zwitterionic Ligands for Long-Term Quantum Dot Bioimaging

Abstract

High colloidal stability in aqueous conditions is a prerequisite for fluorescent nanocrystals, otherwise known as "quantum dots", intended to be used in any long-term bioimaging experiment. This essential property implies a strong affinity between the nanoparticles themselves and the ligands they are coated with. To further improve the properties of the bidentate monozwitterionic ligand previously developed in our team, we synthesized a multidentate polyzwitterionic ligand, issued from the copolymerization of a bidentate monomer and a monozwitterionic one. The nanocrystals passivated by this polymeric ligand showed an exceptional colloidal stability, regardless of the medium conditions (pH, salinity, dilution, and biological environment), and we demonstrated the affinity of the polymer exceeded by 3 orders of magnitude that of the bidentate ligand (desorption rates assessed by a competition experiment). The synthesis of the multidentate polyzwitterionic ligand proved also to be easily tunable and allowed facile functionalization of the corresponding quantum dots, which led to successful specific biomolecules targeting.

Energy Transfer with Semiconductor Quantum Dot Bioconjugates: A Versatile Platform for Biosensing, Energy Harvesting, and Other Developing Applications

“…Increased numbers of anchoring groups are expected to compensate for their inherently weak individual affinity to the QD surface by a collective binding or avidity effect. Polymer backbones used to synthesize these polymeric surface ligands include poly(acrylic acid) (PAA), 194,196 poly(methacrylic acid), 193,195 poly(maleic anhydride), 197 poly(glutamic acid), 198 and poly(aspartic acid). 199 As expected, QDs prepared with thiol-based multidentate polymers exhibited the best colloidal stability across a wide range of pHs while maintaining their hydrodynamic sizes relatively compact in most cases.…”

Quantum dots–DNA bioconjugates: synthesis to applications

“…Based on the nature of synthesis of QDs, types of ligands and nature of reducing agents, variable protocols are optimized [37]. For example, for disulfide containing ligands, prior reduction of the ligands assists in generation of thiol and favours dynamic interactions with the QD surface [38,39]. In the case of some imidazole-or pyridine-based polymers, this reduction step is not required [40,41].…”

Photoligation of an Amphiphilic Polymer with Mixed Coordination Provides Compact and Reactive Quantum Dots

“…[33][34][35][36][37][38][39][40] The multi-coordination interactions between the QD and multidentate ligands decrease the ligand desorption rate from the nanocrystal surfaces, substantially improving the colloidal stability of the QDs in biological media. Nevertheless, thiol-terminated ligands tend to negatively affect the photoluminescence properties of the hydrophilic QDs.…”