DNA nanotechnology-facilitated ligand manipulation for targeted therapeutics and diagnostics.

Ligands, mostly binding to proteins to form complexes and catalyze chemical reactions, can serve as drug and probe molecules, as well as sensing elements. DNA nanotechnology can integrate the high editability of DNA nanostructures and the biological activity of ligands into functionalized DNA nanostructures in a manner of controlled ligand stoichiometry, type, and arrangement, which provides significant advantages for targeted therapeutics and diagnostics. As therapeutic agents, multiple- and multivalent-ligands functionalized DNA nanostructures increase ligand-receptor affinity and activate multivalent ligand-receptor interactions, enabling improved regulation of cell signaling and enhanced control of cell behavior. As diagnostic agents, multiple ligands interaction via DNA nanostructures endows DNA nanosensors with high sensitivity and excellent signal transduction capability. Herein, we review the principles and advantages of using DNA nanostructures to manipulate ligands for targeted therapeutics and diagnostics and provide future perspectives.