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Multivalent particles, i.e. microscopic constructs having multiple ligands,can be used to target surfaces selectively depending on their receptor density.Typically, there is a sharp onset of multivalent binding as the receptordensity exceeds a given threshold. However, the opposite case, selectivelybinding to surfaces with a receptor density below a given threshold, is muchharder. Here, we present a simple strategy for selectively targeting a surfacewith a low density of receptors, within a system also having a surface with ahigher density of the same receptors. Our strategy exploits competitiveadsorption of two species. The first species, called "guards", arereceptor-sized monovalent particles designed to occupy the high-density surfaceat equilibrium, while the second multivalent "attacker" species outcompetes theguards for binding onto the low-density surface. Surprisingly, the recipe forattackers and guards yields more selective binding with strongerligand-receptor association constants, in contrast to standard multivalency. Wederive explicit expressions for the attacker and guard molecular designparameters and concentrations, optimised within bounds of what isexperimentally accessible, thereby facilitating implementation of the proposedapproach.

Multivalent "Attacker & Guard" Strategy for Targeting Surfaces with Low Receptor Density