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

ABSTRACT

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 (Ph ₃ ‐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.