Multivalent interactions in nature are abundant and are of great interest in bioengineering because many biological phenomena such as cell-cell interactions, signaling, cell-matrix binding and immune responses are controlled through multiple weak interactions between ligand-receptor pairs. Nanotechnology has applied this concept to achieve targeted delivery and increase the selectivity of therapeutic and diagnostic nanoparticles. Frenkel’s theory on super-selectivity suggests that a combination of high-valency, low-affinity and flexible particles could achieve a remarkable affinity transition which is promising for the development of targeted therapeutics and sensitive diagnostics.
Although many ligand-presenting multivalent nanoparticles are developed, there is little work to determine whether a specific ligand density to allow for superselective binding exists. The major cause hereof is a lack in nanoparticles’ synthesis and design control in terms of uniform spatial control in ligand presentation.We present a fully programmable DNA-based multivalent nanoparticle platform that can interact with spatially well-defined targets. Ligand valency and spacing on our bivalent backbone is modular and can be controlled with sub-nanometer resolution.