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

Abstract

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.

Nitric oxide-releasing poly(ionic liquid)-based microneedle for subcutaneous fungal infection treatment

“…NO, a biologically active molecule, can diffuse approximately 100 μm under physiological conditions and penetrate cells. 54 To examine the effective cell penetration of NO, DAF-FM DA, an NO fluorescence probe, was used to evaluate the diffusion of NO in fungal cells. Fig.…”

The Role of Nitric Oxide in Stem Cell Biology

“…Additionally, VEGF was conjugated to VEGFR of ECs surface to enhance cellular functions, such as cell survival, migration, and angiogenesis along with NO. Results suggested that this technique on nanocoating-based NO and VEGF co-localization to cells can be beneficial for vascular development in the field of SCs transplantation and organoid platform [131]. A similar study has showed that the encapsulation of the NO-donor S-nitrosoglutathione (GSNO) into chitosan nanoparticles (CS NPs) overcame NO drawbacks in pharmacological applications, such as, its short half-life.…”

“…Since antithrombogenicity is a crucial factor for the long-term success of vascular implants, surface heparinization was further introduced through a stepwise metal (copper)-catechol-(amine) (MCA) surface chemistry strategy. The heparin-grafted and NO-catalytic coating could mimic the physiological functions of native endothelium, which may address the challenges of in-stent restenosis [131].…”

Advanced Nitric Oxide Generating Nanomedicine for Therapeutic Applications

“…Therefore, organic nitrates and nitrites have been used as cardiovascular therapeutic agents to improve the dilation of vascular smooth muscle . Indeed, NO not only has been developed for decades for effective cardiovascular disease therapy but also to improve thromboresistance, antirestenosis, and promote re-endothelialization after stent implantation. − With active ongoing research on the biological mechanism of NO, scientists will surely report more and more NO nanomedicine candidates for the treatment of a variety of additional diseases …”