Nanochemistry Modulates Intracellular Decomposition Routes of S-Nitrosothiol Modified Silica-Based Nanoparticles

Cellular delivery of nitric oxide (NO) using NO donor moieties such as S-nitrosothiol (SNO) is of great interest for various applications. However, understandings of the intracellular decomposition routes of SNO toward either NO or ammonia (NH₃) production are surprisingly scarce. Herein, the first report of SNO modified mesoporous organosilica nanoparticles with tetrasulfide bonds for enhanced intracellular NO delivery, ≈10 times higher than a commercial NO donor, is presented. The tetrasulfide chemistry modulates the SNO decomposition by shifting from NH₃ to NO production in glutathione rich cancer cells. This study provides a new strategy to control the NO level in biological systems.