Smartphone-Guided Visible Light Modulation of RSNOs for Antimicrobial Activity via Controlled Nitric Oxide Release

Methicillin-resistant Staphylococcus aureus (MRSA) remains a major contributor to antimicrobial-resistant infections worldwide. Antimicrobial blue light (aBL, ∼405-450 nm) generates intracellular reactive oxygen species through excitation of endogenous chromophores, while nitric oxide (NO) induces complementary nitrosative and oxidative damage. S-nitrosothiols (RSNOs) provide a platform for visible-light-triggered NO release. Here, a synergistic antimicrobial strategy combining aBL with RSNO coatings was developed to simultaneously generate reactive oxygen and nitrogen species and evaluated against bacterial and fungal pathogens. Four RSNO donors (S-nitroso-N-acetylpenicillamine (SNAP), S-nitrosoglutathione (GSNO), S-nitroso-1-adamantanethiol (SNAT), and S-nitrosotriphenylmethanethiol (Ph₃-CSNO)) were incorporated into catheter insert coatings and exhibited distinct, wavelength-dependent NO-release profiles, with aBL enhancing NO release for all formulations. SNAT showed the greatest photochemical response, with a 235% increase in steady-state NO flux under irradiation. The combined generation of reactive species produced potent broad-spectrum antimicrobial activity against Staphylococcus aureus, MRSA, Escherichia coli, and Candida albicans, achieving >4-log reductions in microbial viability with all RSNO-coated inserts under aBL after 24 h. In vivo, SNAT-coated inserts significantly reduced S. aureus colonization in a rabbit infection model, achieving up to a 2.35-log reduction in bacterial burden, demonstrating that light-triggered NO delivery combined with aBL provides an antibiotic-independent strategy for preventing device-associated infections.