Nanoparticle Bioconjugates: Materials that Benefit from Chemoselective and Bioorthogonal Ligation Chemistries

This chapter presents an overview of the preparation of nanoparticle bioconjugates, illustrated with many representative examples. Nanoparticle materials that are discussed include gold and silver nanoparticles, silica nanoparticles, iron oxide and other magnetic nanoparticles, semiconductor quantum dots, lanthanide nanoparticles, polymer and amphiphile nanoparticles (e.g., liposomes), and carbon allotropes such as carbon nanotubes, graphene and graphene oxide, carbon dots, and fullerenes. Important aspects of the synthesis and chemical functionalization of nanoparticles are summarized, as are important considerations for their bioconjugation: sites for conjugation; intricacies, challenges and opportunities associated with the physical and chemical features of nanoparticles; and the purification and characterization of nanoparticle bioconjugates. Following a brief review of the application of traditional bioconjugate reactions (e.g., carbodiimide coupling, cross-linkers, biotin-avidin) with nanoparticles, the chapter focuses on the growing utilization of chemoselective and bioorthogonal chemistries for the preparation of nanoparticle bioconjugates. These chemistries include azide-alkyne cycloaddition, Diels–Alder reactions, Staudinger ligation, hydrazone and oxime ligation, thiol-ene chemistry, native chemical ligation and intein-assisted conjugation, enzymatic ligation, and affinity and coordinate interactions. The resultant nanoparticle bioconjugates enable applications such as bioanalytical assays, cellular labeling and imaging, diagnostic imaging, and drug delivery and therapy.