Modification of Poly(ethylene glycol)-Capped Quantum Dots with Nickel Nitrilotriacetic Acid and Self-Assembly with Histidine-Tagged Proteins

We describe the design and preparation of luminescent quantum dots (QDs) modified with terminal nickel-nitrilotriacetic acid (Ni-NTA) groups via simple EDC (<i>N</i>-ethyl-<i>N</i>′-(3-dimethylaminopropyl)carbodiimide hydrochloride) condensation, to form QD-Ni-NTA complexes. The QDs were prepared starting from CdSe-ZnS core−shell QDs surface-capped with carboxy-functionalized poly(ethylene glycol) (PEG) ligands. This modification allowed coupling of a controllable number of oligohistidine-tagged proteins via metal-affinity interactions. In particular, QD-Ni-NTA complexes were coupled to 5×His-tagged maltose binding proteins labeled with Texas red, where effective formation of the QD-MBP-Texas red conjugates was confirmed by agarose gel electrophoresis and fluorescence resonance energy transfer studies. The stability of the QD-MBP conjugates was further tested inside live cells following microinjection directly into the cytoplasm. This design expands on the good colloidal stability afforded by our earlier PEG-based modular ligands which provided QDs with great colloidal stability over a broad range of biologically relevant conditions.