Direct Formation of S-Nitroso Silica Nanoparticles from a Single Silica Source

Abstract

Nitric oxide (NO) is a ubiquitous molecule in the body. Because of its multiple pathophysiologic roles, the potential for treating various diseases by the exogenous administration of NO has been under intensive investigation. However, the unstable, radical nature of NO poses a major challenge to the effective delivery of NO. Previously, silica nanoparticles synthesized by the traditional method have been developed into NO-carrying systems. In the present study, for the first time NO-carrying silica nanoparticles were prepared from a single silica precursor using a simple nanoprecipitation method. (3-Mercaptopropyl)-trimethoxysilane (MPTMS) was used as the sole silane source, which was subjected to acid-catalyzed S-nitrosation and condensation reactions in a one-pot organic phase. S-Nitroso silica nanoparticles (SNO-SiNPs) were then produced by injecting a smaller quantity of the organic phase into a larger amount of water without surfactants. Various preparation parameters were tested to obtain optimized conditions. Moreover, a phase diagram demonstrating the ouzo effect was constructed. The prepared SNO-SiNPs were spherical particles with a tunable size in the range of 100-400 nm. The nanoparticles in aqueous dispersions exhibited high colloid stability, possibly resulting from highly negatively charged surfaces. The result of solid-state (29)Si NMR shows the predominance of T(2) and T(3) silicon structures, suggesting that nanoparticles were formed from polycondensed silica species. In conclusion, NO-loaded silica nanoparticles have been directly prepared from a single silane precursor using a surfactant-free, low-energy, one-step nanoprecipitation approach. The method precludes the need for the initial formation of bare particles and subsequent functionalization steps.

Hollow polymer nanoparticles with S-nitrosothiols as scaffolds for nitric oxide release

“…With respect to the various triggers (e.g., light, ascorbate, temperature, copper, etc.) previously mentioned in the literatures [2,8,13,16], the copper trigged release characters of the hollow S-nitrosothiol nanoparticles were determined in this present work. Previous researches implied that the mechanism of S-nitrosothiol NO donor decomposition was mediated via the Cu + /Cu 2+ redox cycle and copper-containing enzymatic metal centers [13,27,28].…”

“…The hollow S-nitrosothiol polymer nanoparticles were prepared according to the procedure reported by the previous literature [2,8,16]. 50 mg P(EGDMA-co-HEMA)-SH nanoparticles were added to 10 mL of methanol/H 2 O (V/V, 1/1) at 0°C under stirring.…”

“…Nitric oxide (NO), which is naturally produced by endothelial cells in bodies, plays multifaceted biological functions in cardiovascular, respiratory, and nervous systems [1][2][3]. From cardiovascular regulation to antimicrobial and tumoricidal therapies, deficiencies in NO biosynthesis have been linked to a number of disease states due to the role of NO in human physiology [3,4].…”

“…As NO is a highly reactive and unstable molecule, it is necessary to develop methods for chemically storing and releasing NO in a controlled manner. In the past decades, numerous NO donors have been synthesized such as metal complexes [5], nitrosoamines [6], diazeniumdiolates [7], and S-nitrosothiols [2]. Among them, S-nitrosothiols (RSNOs) NO donors have received much attention recently due to their low toxicity compared to the other NO donor precursors [8].…”

“…Some low molecularweight RSNOs, such as S-nitrosoglutathione and S-nitrosocysteine have been proposed as mediators of paracrine protein S-nitrosylation [14]. A class of S-nitroso silica nanoparticles generated by Hu and coworkers exhibited a lengthy duration of NO release with a half-life (t 1/2 ) of 10 h under physiological conditions, which utilized (3-mercaptopropyl)-trimethoxysilane (MPTMS) as the sole silane source subjected to acid-catalyzed S-nitrosation and condensation reactions [2]. Enzymatically degradable nitric oxide (NO) releasing S-nitrosated dextran thiomers were developed as potent biomedical materials with the NO storage capacity of about 0.2 mmol/g [15].…”