Polydopamine-Coated Selenium Nanoparticles as a Stable Catalyst for Tunable and Sustained Nitric Oxide Generation.

Nitric oxide (NO) is a therapeutic gas molecule involved in numerous physiological and pathological processes. However, its clinical application is limited by its short half-life and limited diffusion distance in human tissues, necessitating the development of effective NO delivery strategies. In situ NO generation via catalytic decomposition of endogenous NO donors has emerged as a promising approach. Selenium nanoparticles (SeNPs) have demonstrated high catalytic efficiency for NO generation with low cytotoxicity, but their performance is hindered by poor stability under physiological conditions and pH-dependent activity. To address these limitations, in this study, selenium-polydopamine core-shell nanoparticles (Se@PDA NPs) are developed to improve catalytic stability and mitigate pH sensitivity. The PDA coating enables consistent NO delivery across a broad pH range (5.5-8.5), expanding their therapeutic potential. NO generation is tunable by varying the PDA coating thickness, and the nanoparticles exhibit excellent biocompatibility and enhanced cellular uptake. In human coronary artery smooth muscle cells, Se@PDA NPs catalyze intracellular NO generation from endogenous S-nitrosothiols and promote the formation of multicellular aggregates, indicating potential activation of intercellular communication. The Se@PDA NPs maintain sustained NO generation over five doses and remain active for at least two months, demonstrating strong potential for NO-based therapies.