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S-nitrosocaptopril Nanoparticles as Nitric Oxide-Liberating and Transnitrosylating Anti-infective Technology

TitleS-nitrosocaptopril Nanoparticles as Nitric Oxide-Liberating and Transnitrosylating Anti-infective Technology
Publication TypeJournal Article
Year of Publication2014
AuthorsMordorski B, Pelgrift R, Adler B, Krausz A, Neto ABatista da, Liang H, Gunther L, Clendaniel A, Harper S, Friedman JM, Nosanchuk JD, Nacharaju P, Friedman AJ
Date Published2014 Nov 15

Nitric oxide (NO) is an essential agent of the innate immune system which exhibits multi-mechanistic antimicrobial activity. Previously, NO-releasing nanoparticles (NO-np) demonstrated increased antimicrobial activity when combined with glutathione (GSH), versus NO-np alone, due to formation of S-nitrosoglutathione (GSNO), a transnitrosylating agent. To capitalize on this finding, we incorporated the thiol-containing ACE-inhibitor, captopril, into the NO-np system 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 coli and methicillin-resistant Staphylococcus aureus were highly susceptible to SNO-CAP-np in a dose-dependent fashion, with E. coli being 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. coli susceptibility compared to NO-np, transnitrosylation rather than free NO is likely responsible for overcoming E. coli's resistance mechanisms and ultimately killing the pathogen.

Alternate JournalNanomedicine
PubMed ID25461287

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