S-nitrosocaptopril nanoparticles as nitric oxide-liberating and transnitrosylating anti-infective technology

Nitric oxide (NO), an essential agent of the innate immune system, exhibits multi-mechanistic antimicrobial activity. Previously, NO-releasing nanoparticles (NO-np) demonstrated increased antimicrobial activity when combined with glutathione (GSH) due to formation of S-nitrosoglutathione (GSNO), a transnitrosylating agent. To capitalize on this finding, we incorporated the thiol-containing ACE-inhibitor, captopril, with NO-np to form SNO-CAP-np, nanoparticles that both release NO and form S-nitrosocaptopril. In the presence of GSH, SNO-CAP-np demonstrated increased transnitrosylation activity compared to NO-np, as exhibited by increased GSNO formation.. Escherichia coliand methicillin-resistant. Staphylococcus aureuswere highly susceptible to SNO-CAP-np in a dose-dependent fashion, with. E. colibeing most susceptible, and SNO-CAP-np were nontoxic in zebrafish embryos at translatable concentrations. Given SNO-CAP-np's increased transnitrosylation activity and increased. E. colisusceptibility compared to NO-np, transnitrosylation rather than free NO is likely responsible for overcoming. E. coli's resistance mechanisms and ultimately killing the pathogen.