Nucleic acid-passivated semiconductor nanocrystals: biomolecular templating of form and function.
Bright, photostable luminescent labels are powerful tools for the in vitro and in vivo imaging of biological events. Semiconductor nanocrystals have emerged as attractive alternatives to commonly used organic lumophores because of their high quantum yields and the spectral tunability that can be achieved through synthetic control. Although conventional synthetic methods generally yield high-quality nanocrystals with excellent optical properties for biological imaging, ligand exchange and biological conjugation are necessary to make nanocrystals biocompatible and biospecific. These steps can substantially deteriorate the optical characteristics of these nanocrystals. Moreover, the complexity of multistep nanocrystal synthesis, typically requiring inert and anhydrous conditions, prohibits many end users of these lumiphores from generating their own custom materials. We sought to streamline semiconductor nanocrystal synthesis and develop synthetic routes that would be accessible to scientists from all disciplines. In search of such an approach, we turned to nucleic acids as a programmable and versatile ligand set and found that these biomolecules are indeed appropriate for biocompatible semiconductor nanocrystals preparation. In this Account, we summarize our work on nucleic acids-programmed nanocrystal synthesis that has resulted in the successful development of a one-step synthesis of biofunctionalized nanocrystals in aqueous solution. We first discuss results obtained with nucleotide-capped cadmium and lead chalcogenide-based nanocrystals that served to guide further investigation of polynucleotide-assisted synthesis. We investigated the roles of individual nucleobases and their structures in passivation of the surfaces of nanocrystals and modulating morphology and optical characteristics. The nucleic acid structures and sequences and the reaction conditions greatly influence the nanocrystals' optical properties and morphologies. Moreover, studies using live cells reveal low toxicity and rapid uptake of DNA-passivated CdS nanocrystals, demonstrating their suitability for bioimaging. Finally, we describe a new approach that leads to the production of biofunctionalized, DNA-capped nanocrystals in a single step. Chimeric DNA molecules enable this strategy, providing both a domain for nanocrystal passivation and a domain for biomolecule recognition. Nanocrystals synthesized using this approach possess good spectral characteristics as well as high specificity to cognate DNA, protein, and cancer cell targets. Overall, this approach could make nanocrystal lumiphores more readily accessible to researchers working in the biological sciences.
Ma
Nan
N
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
Tikhomirov
Grigory
G
Kelley
Shana O
SO
D001483:Base Sequence; D019187:Cadmium Compounds / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009696:Nucleic Acids / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D045663:Quantum Dots; D013440:Sulfides / Q000737:chemistry
D019187:Cadmium Compounds; D008024:Ligands; D009696:Nucleic Acids; D013440:Sulfides; C034939:cadmium sulfide