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

## TL;DR

This paper introduces a novel multivalent strategy using competitive adsorption of 'attacker' and 'guard' particles to selectively target surfaces with low receptor density, overcoming limitations of traditional multivalent binding.

## Contribution

The authors develop a simple, experimentally feasible method for targeting low-density receptor surfaces using a dual-species approach, with explicit design parameters and optimized conditions.

## Key findings

- Enhanced selectivity for low-density surfaces demonstrated
- Stronger ligand-receptor affinity improves targeting efficiency
- Explicit design equations facilitate experimental implementation

## Abstract

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 receptor density exceeds a given threshold. However, the opposite case, selectively binding to surfaces with a receptor density below a given threshold, is much harder. Here, we present a simple strategy for selectively targeting a surface with a low density of receptors, within a system also having a surface with a higher density of the same receptors. Our strategy exploits competitive adsorption of two species. The first species, called "guards", are receptor-sized monovalent particles designed to occupy the high-density surface at equilibrium, while the second multivalent "attacker" species outcompetes the guards for binding onto the low-density surface. Surprisingly, the recipe for attackers and guards yields more selective binding with stronger ligand-receptor association constants, in contrast to standard multivalency. We derive explicit expressions for the attacker and guard molecular design parameters and concentrations, optimised within bounds of what is experimentally accessible, thereby facilitating implementation of the proposed approach.