Gelatin–siloxane nanoparticles to deliver nitric oxide for vascular cell regulation: Synthesis, cytocompatibility, and cellular responses

Abstract

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.

Antimicrobial Activity of Nitric Oxide-Releasing Ti-6Al-4V Metal Oxide

“…NO release from S -nitroso-penicillamine-modified Ti-6Al-4V was monitored over 48 h using the Griess assay [23,37]. Briefly, three coupons of S -nitroso-penicillamine-modified Ti-6Al-4V were added to three separate vials containing 900 μL of PBS and placed on an incubator/shaker at 37 °C, while protected from light.…”

Combating atherosclerosis with targeted nanomedicines: recent advances and future prospective

“…Zhang et al applied gelatin–siloxane (GS) NPs to deliver nitric oxide (NO) to vascular cells in order to regulate the vascular cell behavior and prevent restenosis. 17 , 86 Acid orange 7 (AO7) assay was applied to quantify amino groups on GS NPs. After preparing NO-releasing S-nitrosothiol (RSNO) modified GS NPs (GS-NO NPs), they were subjected to size determination.…”

Modulated nitric oxide delivery in three-dimensional biomaterials for vascular functionality

“…The NO payload could reach 11.26 µM/mg, and the release could last for 101 h with a half-life of 253 min. Recently, Zhang et al [87] reported a cytocompatible NO-releasing NP synthesized via thiolation of gelatin-siloxane NPs. The resultant NO-releasing NPs (GS-NO NPs) could release NO following a first-order exponential profile (∼0.12 µM/mg within 7 days), and could realize rapid intracellularization within 2 h. In vitro study with human aortic SMCs and human umbilical vein ECs suggested that GS-NO NPs could exhibit a dose-dependent effect for inhibited SMCs proliferation and promoted ECs proliferation, with great potential of preventing vascular restenosis.…”