Novel E-Selectin Binding Polymers Reduce Atherosclerotic Lesions in ApoE^(-/-) Mice

Atherosclerosis is characterized by chronic vascular inflammation and leucocyte recruitment through E-selectin adhesion molecule, leading to plaque progression and destabilization. We hypothesized that E-selectin-targeted novel N-(2-hydroxypropyl)-meth-acrylamide (HPMA) polymers bearing the anti-inflammatory drug dexamethasone would prevent vascular inflammation and plaque progression. E-selectin binding polymers with and without dexamethasone (P-ESBP-Dex and P-ESBP) were delivered IP to western diet-fed ApoE^(-/-) mice. To assess plaque growth we used a novel Vevo Vasc software application designed to measure in-vivo vessel wall anatomy and motion in small-animal models. Our data showed that both P-ESBP and P-ESBP-Dex selectively targeted atherosclerotic lesions and reduced ascending aorta wall thickness. Furthermore, the addition of dexamethasone to the polymers did not improve their therapeutic effect. Our findings suggest a novel nanomedicine-based strategy to treat atherosclerosis and stabilize vulnerable plaque.