Nanoparticle targeting using multivalent ligands: computer modeling

Abstract

Using Monte Carlo simulations, we analyze the efficiency in targeting mobile receptors on cell surfaces by nanoparticles carrying multivalent (divalent, tetravalent) ligands. We show that in most cases the nanoparticles with multivalent ligands exhibit very minor or no advantage in cell surface targeting compared to nanoparticles functionalized with monovalent ligands with the same density of functional groups, as in both cases nanoparticles can interact with a receptor surface in a multivalent manner. We identify a few cases when using multivalent ligands in nanoparticle targeting can be beneficial, especially for a high binding energy of ligand–receptor interactions and large receptor densities. We demonstrate that for nanoparticles with longer tether length or larger core size, where the entropic loss for stretching tethers carrying ligands is significant, the possibility to deliver the same number of functional groups to a cell surface by using a smaller number of ligated tethers, as in the case of using multivalent ligands, becomes favorable. We also show that multivalent ligands can enhance the selectivity of nanoparticle targeting by increasing the nanoparticle affinity to cells with a high density of mobile receptors. The obtained results provide guidance for the experimental development of targeted nanoparticles with multivalent ligands for imaging and therapeutic applications.