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

Breanne Mordorski, Robert Pelgrift, Brandon Adler, Aimee Krausz, Alexandre Batista da Costa Neto, Hongying Liang, Leslie Gunther, Alicea Clendaniel, Stacey Harper, Joel M. Friedman, Joshua D. Nosanchuk, Parimala Nacharaju, Adam J. Friedman

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)283-291
Number of pages9
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2015

Keywords

  • Antibacterial
  • E. coli
  • Nanotechnology
  • Nitric oxide
  • Nitrosothiols

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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  • Cite this

    Mordorski, B., Pelgrift, R., Adler, B., Krausz, A., da Costa Neto, A. B., Liang, H., Gunther, L., Clendaniel, A., Harper, S., Friedman, J. M., Nosanchuk, J. D., Nacharaju, P., & Friedman, A. J. (2015). S-nitrosocaptopril nanoparticles as nitric oxide-liberating and transnitrosylating anti-infective technology. Nanomedicine: Nanotechnology, Biology, and Medicine, 11(2), 283-291. https://doi.org/10.1016/j.nano.2014.09.017