Tertiary <i>S</i>-Nitrosothiol Functionalized Mesoporous Silica Nanoparticles for Nitric Oxide Delivery

The exogenous delivery of nitric oxide (NO) as a therapeutic is challenging due to NO’s high reactivity and short half-life. Owing to NO’s many physiological functions, the development of NO-releasing materials for sustained and long-term NO delivery has been a focus of much research. Herein, we report the synthesis of an organosilane bestowing a tertiary thiol (3° SH) moiety derived from (3-aminopropyl)trimethoxysilane and N-acetyl-d-penicillamine thiolactone (NAP-thiolactone). The resulting tertiary thiol-bearing organosilanes (NAPTMS) were covalently tethered to mesoporous silica nanoparticles (MSNs) to generate 3° SH-enriched MSNs (MSN-NAP) that, when nitrosated, formed NO-releasing mesoporous silica nanoparticles (MSN-SNAP). The morphological and thermomechanical properties of MSN-NAP and MSN-SNAP proved suitable as potential therapeutic materials, with NO payloads (1.39 ± 0.15 μmol mg–1) approximately ten times greater than previously reported tertiary S-nitrosothiol (3° RSNO) systems. In contrast to other reports, MSN-SNAP exhibits a sustained NO-release profile for >24 h under physiological conditions. The MSN-SNAP thus represents a promising NO-releasing prodrug for various biomedical applications that require sustained NO delivery at low concentrations (pM to nM).