Multivalent conjugation of peptides, proteins, and DNA to semiconductor quantum dots

Semiconductor nanocrystals or quantum dots (QDs) have become well-established as a unique nanoparticle scaffold for bioapplications due to their robust luminescent properties. In order to continue their development and expand this technology, improved methodologies are required for the controllable functionalization and display of biomolecules on QDs. In particular, efficient routes that allow control over ligand loading and spatial orientation, while minimizing or eliminating cross-linking and aggregation are needed. Two conjugation approaches are presented that address these needs: (1) polyhistidine-based metal-affinity self-assembly to QD surfaces and (2) carbodiimide-based amide bond formation to carboxy-functionalized polyethylene glycol or PEGylated QDs. These approaches can be successfully employed in the construction of a variety of QD-biomolecule constructs utilizing synthetic peptides, recombinant proteins, peptides, and even modified DNA oligomers.