Optimal multivalent targeting of membranes with many distinct receptors

Significance A key challenge in biomedical research is the ability to specifically target cells and tissues. Targeting typically relies on identifying a suitable marker, e.g., a highly expressed receptor, and choosing a ligand that strongly and specifically binds to the marker. However, this procedure fails when a suitable marker unique to the targeted cells cannot be identified, notably in many forms of cancer. We show that properly designed multivalent targeting of multiple cognate receptor types results in a specificity toward a chosen receptor density profile, thus demonstrating a general route toward targeting cells without particularly dominant markers.