Architectural and structural optimization of the protective polymer layer for enhanced targeting.

Using Monte Carlo simulations we study the influence of ligand architecture (valence, branching length) and structure (polydispersity) of a flat protective polymer layer on the accessibility of its functional groups and efficiency of receptor targeting. Two types of receptor surfaces were considered: the surface homogeneously covered with receptors and the surface containing a finite number of receptor sites. We found that multivalent ligands provide a larger density of targeting groups on the periphery of the layer compared to monovalent ligands for the same overall number of targeting groups per polymer layer. Because of their cooperativity in binding, multivalent ligands were also considerably more efficient in binding to both types of receptor surfaces. With an increase of ligand valence the number of functional groups attached to receptors noticeably increases. Short-branched divalent ligands show an especially high cooperativity in binding to closely packed receptors. However, in the case of immobile receptors separated by a finite distance from each other, the average distance between the functional groups belonging to the same short divalent ligand is too small to reach different receptors simultaneously and the receptor binding is less efficient than in the monovalent ligand case. Using a bidisperse protective polymer layer formed by short nonfunctional polymers and long functionalized polymers considerably increases the fraction of functional groups on the periphery of the layer. Simulations of receptor binding confirm the high efficiency of receptor targeting by bidisperse polymer layers, which is achieved by means of larger compressibility and higher capability of the ligands to reach out compared to the corresponding monodisperse layers. The concepts of multivalent ligands and a bidisperse protective polymer layer each have their own advantages which can be combined for an enhanced targeting effect.