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Gelatin-siloxane nanoparticles to deliver nitric oxide for vascular cell regulation: synthesis, cytocompatibility, and cellular responses.

Nitric oxide (NO) is an important mediator in cardiovascular system to regulate vascular tone and maintain tissue homeostasis. Its role in vascular cell regulation makes it promising to address the post-surgery restenosis problem. However, the application of NO is constrained by its high reactivity. Here, we developed a novel NO-releasing gelatin-siloxane nanoparticle (GS-NO NP) to deliver NO effectively for vascular cell regulation. Results showed that gelatin-siloxane nanoparticles (GS NPs) could be synthesized via sol-gel chemistry with a diameter of ∼200 nm. It could be modified into GS-NO NPs via S-nitrosothiol (RSNO) modification. The synthesized GS-NO NPs could release a total of ∼0.12 µmol/mg NO sustainably for 7 days following a first-order exponential profile. They showed not only excellent cytocompatibility, but also rapid intracellularization within 2 h. GS-NO NPs showed inhibition of human aortic smooth muscle cell (AoSMC) proliferation and promotion of human umbilical vein endothelial cell (HUVEC) proliferation in a dose-dependent manner, which is an important approach to prevent restenosis. With GS-NO NP dose at 100 µg/mL, the proliferation of AoSMCs could be slowed down whereas the growth of HUVECs was significantly promoted. We concluded that GS-NO NPs could have potential to be used as a promising nano-system to deliver NO for vascular cell regulation.