4.7 Article

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

Journal

ADVANCED HEALTHCARE MATERIALS
Volume 11, Issue 6, Pages -

Publisher

WILEY
DOI: 10.1002/adhm.202102095

Keywords

angiogenesis; cell coating; human vein endothelial cells; layer-by-layer assembly; nitric oxide delivery; vascular endothelial growth factors

Funding

  1. National Research Foundation of Korea (NRF) - Ministry of Science and ICT [NRF-2017R1E1A1A01074343]

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The study utilizes a nanocoating technology for direct delivery of nitric oxide (NO) to individual endothelial cells, with the additional application of VEGF to enhance angiogenic activation. The synergistic effect of NO and VEGF via nanocoating significantly improves survival and proliferation of endothelial cells, as well as promotes cell migration and tubule formation for angiogenesis. This unique technology demonstrates great potential in enhancing desired angiogenic functions in individual endothelial cells through efficient NO delivery.
The delivery of nitric oxide (NO)-an intrinsic cellular signaling molecule-is promising for disease treatment, in particular to vascular diseases, due to its endothelial-derived inherent nature. The limited diffusion distance of labile NO prompts researchers to develop various carriers and targeting methods for specific sites. In contrast to the apoptotic effect of NO, such as anticancer, delivering low NO concentration at the desired targeting area is still intricate in a physiological environment. In this study, the layer-by-layer assembled nanocoating is leveraged to develop a direct NO delivery platform to individual endothelial cells (ECs). NO can be localized to individual ECs via S-nitrosothiol-bound polyacrylic acid which is a polymer directly providing an endothelial-like constant level of NO. To increase angiogenic activation along with NO, VEGF is additionally applied to specific receptors on the cell surface. Notably, the survival and proliferation of ECs are significantly increased by a synergistic effect of NO and VEGF co-localized via nanocoating. Furthermore, the nanocoating remarkably promoted cell migration and tubule formation-prerequisites of angiogenesis. The proposed unique technology based on nanocoating demonstrates great potential for conferring desired angiogenic functions to individual ECs through efficient NO delivery.

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