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A Nanocoating Co-Localizing Nitric Oxide and Growth Factor onto Individual Endothelial Cells Reveals Synergistic Effects on Angiogenesis

Nitric oxide (NO) is an intrinsic cell signaling molecule that is expected to be used in disease treatment, especially vascular disease, due to its inherent endothelium-derived properties. The limited diffusion distance of unstable NO has prompted researchers to develop various vectors and targeting methods for specific loci. In contrast to the apoptotic effects of NO (e. g., anticancer), the delivery of low concentrations of NO in the desired targeted region is still complex in a physiological context. In this study, layer-by-layer assembled nanocoatings were used to develop a platform for delivering NO delivery directly to single endothelial cells (EC). NO can be localized by S to a single EC-nitrosothiol-bound polyacrylic acid, a polymer that directly provides endothelial-like constant levels of NO. To work together with NO to increase angiogenic activation, VE GF was additionally applied to specific receptors on the cell surface. Notably, the synergistic effect of colocalization of NO and VE GF through the nanocoating significantly increased EC survival and proliferation. Moreover, the nanocoating significantly promoted cell migration and tubule formation — a prerequisite for angiogenesis. The proposed unique nanocoating-based technology demonstrates the great potential of conferring the desired angiogenic function to a single EC through efficient NO delivery.