Improving the binding efficiency of a vascular drug delivery system by using a dual-receptor targeting strategy

Abstract

Targeted drug delivery offers several advantages with respect to conventional delivery methods including reduced side effects and lower drug doses. However, the delivery efficiency is significantly affected by the choice of the target epitopes that selectively interact with endothelial cells located in inflammatory sites. In this study we present a novel dualreceptor targeting approach to enhance the drug carrier's binding efficiency to the inflamed diseased tissue. Dual-receptor targeted drug carriers were prepared by coating polymer microspheres with different molar ratios of antibodies against ICAM-1 (aICAM-1) and E-selectin (aEselectin). A flow chamber was used to study the interaction of the microspheres with TNF-α activated HUVECs under different flow conditions.Our experimental results shows that our dual-receptor targeted drug carriers have significantly higher binding efficacy compared to single-receptor targeted drug carriers. Moreover, we found that the optimal ratio of aICAM-1:aE-selectin for binding efficacy is 70:30. The level of adhesion of our carriers appeared to decrease with increase in wall shear stress.We conclude that the adhesion efficiency of the dual-receptor targeting system is significantly higher than the single-receptor. Moreover, the drug carrier adhesion ability can be improved by optimizing the ratio of the two receptors on the surface of the microspheres.

Hyaluronic acid and Arg-Gly-Asp peptide modified Graphene oxide with dual receptor-targeting function for cancer therapy

“…24 Additionally, several studies have indicated that synergic effects can be achieved by creating dual receptor-targeted drug delivery system (e.g. polymeric micelle, nanoparticle, microspheres, etc), [32][33][34] which is more efficient for tumor-specific delivery of anticancer drugs than their corresponding single receptor targeting systems. [35][36][37] In this study, we designed a novel graphene oxidebased carrier (GO-HA-RGD/Dox) with high stability and tumor targeting, high drug loading capacity and pH-dependent drug release in the cancer site.…”

Bivalent engagement of endothelial surface antigens is critical to prolonged surface targeting and protein delivery in vivo

“…The vascular endothelium is a critical site for therapeutic action in a variety of human diseases, 1 in large part because of the numerous physiologic functions of the endothelial monolayer and the consequences of dysfunction and/or injury to these pleiotropic cells. 2 The concept of targeting drugs or drug carriers to endothelial surface molecules has been advanced by a number of laboratories over the past several decades, but most applications have focused on either transcytosis (ie, using affinity ligands to induce transport across the endothelium) or delivery of therapeutics into endothelial cells, with the goal of modulating intracellular signaling pathways and/or gene expression. Less attention has been paid to the possibility of targeting the endothelial surface, where integral membrane proteins project into the bloodstream and modulate coagulation, fibrinolysis, barrier function, and the adhesion of circulating blood cells.…”