TY - JOUR
T1 - S-nitrosocaptopril nanoparticles as nitric oxide-liberating and transnitrosylating anti-infective technology
AU - Mordorski, Breanne
AU - Pelgrift, Robert
AU - Adler, Brandon
AU - Krausz, Aimee
AU - da Costa Neto, Alexandre Batista
AU - Liang, Hongying
AU - Gunther, Leslie
AU - Clendaniel, Alicea
AU - Harper, Stacey
AU - Friedman, Joel M.
AU - Nosanchuk, Joshua D.
AU - Nacharaju, Parimala
AU - Friedman, Adam J.
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - 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.
AB - 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.
KW - Antibacterial
KW - E. coli
KW - Nanotechnology
KW - Nitric oxide
KW - Nitrosothiols
UR - http://www.scopus.com/inward/record.url?scp=84922772298&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922772298&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2014.09.017
DO - 10.1016/j.nano.2014.09.017
M3 - Article
C2 - 25461287
AN - SCOPUS:84922772298
SN - 1549-9634
VL - 11
SP - 283
EP - 291
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
IS - 2
ER -