Designing multivalent probes for tunable superselective targeting

Significance A basic requirement in biomedical research is the ability to specifically target cells and tissues. Targeting typically relies on the specific binding of a “ligand” on a tailor-made probe to a “receptor” on the desired cell/tissue. Conventional probes efficiently distinguish a biological entity displaying the receptor from others that do not, but exhibit limited selectivity when the entities to be distinguished display a given receptor at different densities. Multivalent probes that bind several receptors simultaneously potentially can sharply discriminate between different receptor densities. We demonstrate how such “superselective” binding can be tuned through probe design to target a desired receptor density, and thus lay the foundation for the rational design of a new generation of analytical, diagnostic, and therapeutic probes.