Targeted polyelectrolyte complex micelles treat vascular complications in vivo.

Vascular disease is a leading cause of morbidity and mortality in the United States and globally. Pathological vascular remodeling, such as atherosclerosis and stenosis, largely develop at arterial sites of curvature, branching, and bifurcation, where disturbed blood flow activates vascular endothelium. Current pharmacological treatments of vascular complications principally target systemic risk factors. Improvements are needed. We previously devised a targeted polyelectrolyte complex micelle to deliver therapeutic nucleotides to inflamed endothelium in vitro by displaying the peptide VHPKQHR targeting vascular cell adhesion molecule 1 (VCAM-1) on the periphery of the micelle. This paper explores whether this targeted nanomedicine strategy effectively treats vascular complications in vivo. Disturbed flow-induced microRNA-92a (miR-92a) has been linked to endothelial dysfunction. We have engineered a transgenic line (miR-92aEC-TG /Apoe-/- ) establishing that selective miR-92a overexpression in adult vascular endothelium causally promotes atherosclerosis in Apoe-/- mice. We tested the therapeutic effectiveness of the VCAM-1-targeting polyelectrolyte complex micelles to deliver miR-92a inhibitors and treat pathological vascular remodeling in vivo. VCAM-1-targeting micelles preferentially delivered miRNA inhibitors to inflamed endothelial cells in vitro and in vivo. The therapeutic effectiveness of anti-miR-92a therapy in treating atherosclerosis and stenosis in Apoe-/- mice is markedly enhanced by the VCAM-1-targeting polyelectrolyte complex micelles. These results demonstrate a proof of concept to devise polyelectrolyte complex micelle-based targeted nanomedicine approaches treating vascular complications in vivo.

Water-polyamide chemical interplay in desalination membranes explored by ambient pressure X-ray photoelectron spectroscopy.

Reverse osmosis using aromatic polyamide membranes is currently the most important technology for seawater desalination. The performance of reverse osmosis membranes is highly dependent on the interplay of their surface chemical groups with water and water contaminants. In order to better understand the underlying mechanisms of these membranes, we study ultrathin polyamide films that chemically resemble reverse osmosis membranes, using ambient pressure X-ray photoelectron spectroscopy. This technique can identify the functional groups at the membrane-water interface and allows monitoring of small shifts in the electron binding energy that indicate interaction with water. We observe deprotonation of free acid groups and formation of a 'water complex' with nitrogen groups in the polymer upon exposure of the membrane to water vapour. The chemical changes are reversed when water is removed from the membrane. While the correlation between functional groups and water uptake is an established one, this experiment serves to understand the nature of their chemical interaction, and opens up possibilities for tailoring future materials to specific requirements.