Recent progress in the bioconjugation of quantum dots

Abstract The utility of luminescent semiconductor quantum dots (QDs) in biological applications is directly dependent upon their ability to undergo bioconjugation to proteins, peptides, DNA, drugs and indeed all other manner of biomolecules. In this focused review, we provide an overview of the diverse chemistries that are used for these purposes, including a special emphasis on recent progress by our groups toward optimizing or developing new chemistries. We begin by examining the characteristics and activity ideally desired from QD-bioconjugates, along with the linkage chemistries that are most often utilized. The utility of polyhistidine-mediated metal-affinity coordination to QD surfaces or surface functionalizing ligands is then described in detail. This particular conjugation approach is highly desirable due to its functional simplicity and the control it can afford over the final QD-bioassembly. A variety of other modular, chemoselective ligation chemistries that can be applied either directly on the QD or to the biological to facilitate subsequent QD assembly are described, including aniline-catalyzed imine ligation, thiol-exchange, thiol-targeting iodoacetate chemistry, and Cu(I)-catalyzed azide-alkyne cycloaddition. Commercial QD labeling chemistries that incorporate some of these bioconjugation approaches are also highlighted. Due to their continued widespread use, bioconjugation routes that target the QD surface functionalizing and solubilizing ligands are covered, as are improvements in their functional implementation. Selected examples of applications that incorporate QD-bioconjugates assembled using the different chemistries described are included where appropriate, along with discussion of their benefits and liabilities within that application. Finally, a perspective on remaining issues and how this field will evolve is offered.