Synthesis of nitric oxide-releasing silica nanoparticles

The synthesis and characterization of a new nitric oxide (NO)-releasing scaffold prepared from amine-functionalized silica nanoparticles are reported. Inorganic-organic hybrid silica was prepared via cocondensation of tetraethoxy- or tetramethoxysilane (TEOS or TMOS) and aminoalkoxysilane with appropriate amounts of ethanol (or methanol), water, and ammonia. The amine functional groups in the silica were converted to N-diazeniumdiolate NO donors via exposure to high pressures of NO (5 atm) under basic conditions. Control over both the structure and concentration of the silane precursors (i.e., tetraalkoxy- and aminoalkoxysilanes) and specific synthetic conditions allowed for the preparation of NO donor silica particles of widely varying sizes (d = 20-500 nm), NO payloads (50-1780 nmol.mg-1), maximum amounts of NO released (10-5500 ppb.mg-1), half-lives (0.1-12 h), and NO release durations (up to 30 h). The silica nanoparticles were characterized by solid-state 29Si nuclear magnetic resonance (NMR), atomic force microscopy (AFM), elemental analysis, and gas adsorption-desorption isotherms. The advantages of silica-derived NO storage/delivery systems over previously reported macromolecular NO donors include the ability to (1) store large quantities of NO, (2) modulate NO release kinetics, and (3) readily tune particle size based on the composition of the particle. In addition, a one-pot strategy for preparing the NO donor silica allows for straightforward, high-throughput synthesis and purification.