Multivalent DNA Nanostructures: A Recognition-Anchoring-Functionalization Framework for Precision Theranostics

The programmable engineering of cell membranes is pivotal for precision medicine, yet it remains challenging due to the limitations of natural systems and conventional synthetic tools. Multivalent interactions, ubiquitous in nature, offer a blueprint for enhanced binding avidity and specificity, but replicating this complexity synthetically has been difficult. DNA nanotechnology emerges as a transformative platform, enabling the construction of multivalent scaffolds with atomic-level precision. This review introduces a unified “Recognition-Anchoring-Functionalization” framework to systematize recent advances. We first elucidate the “Recognition” principles of multivalent DNA nanostructures, highlighting their superiority over monovalent probes. We then compare the applicability of the two “Anchoring” strategies, namely in situ and ex situ synthesis. Finally, we showcase “Functionalization” through transformative applications in sensing, immune engineering, and targeted therapy. This framework positions multivalent DNA nanostructures as cornerstones for the development of dynamic, intelligent living medicines, charting a clear path from fundamental design to clinical translation.