Reducing Ischemia/Reperfusion Injury by the Targeted Delivery of Nitric Oxide from Magnetic-Field-Induced Localization of S-Nitrosothiol-Coated Paramagnetic Nanoparticles

Mahantesh S. Navati, Alfredo Lucas, Celine Liong, Marcelo Barros, Jyothishree Tholalu Jayadeva, Joel M. Friedman, Pedro Cabrales

Research output: Contribution to journalArticle

Abstract

Nitric oxide (NO) is an important factor during an ischemia/reperfusion (I/R) injury. Protective actions of NO during I/R are attributed to antioxidant and anti-inflammatory effects, as well as cell-signaling-based inhibition of nuclear proteins. The therapeutic potential of supplemented NO during I/R is nonetheless uncertain, since peroxynitrite formed from NO near superoxide can be potentially harmful due to NF-κB up-regulation and direct cytotoxicity. This study investigates new technology to provide the magnet-assisted delivery of therapeutic levels of localized NO to targeted I/R tissues using biocompatible gadolinium-oxide-based paramagnetic nanoparticles coated with S-nitrosothiols (SNO-PMNPs). Hamsters fitted with a window chamber were subjected to ischemia by application of a tourniquet at the periphery of the window chamber for 1 h. The SNO-PMNPs were intravenously infused (10 mg/kg) during the reperfusion phase, during which time a localized external magnetic field was either applied or not applied to the I/R area. The microvascular hemodynamics, functional capillary density (FCD), rolling and adherent leukocytes, reactive oxygen and nitrogen species, and tissue viability were assessed using intravital microscopy. Control animals did not receive SNO-PMNPs. Treatment with SNO-PMNPs plus a magnet but not without a magnet increased reflow, decreased leukocytes rolling and sticking in postcapillary venules, limited cell death, and restored the FCD. The absence of the magnet resulted in systemic changes in heart rate and mean arterial blood pressure, consistent with the systemic delivery of NO by the SNO-PMNP. These results indicate that the localized delivery of NO during reperfusion counters the deleterious consequences of peroxynitrite and other reactive species generated upon reperfusion as reflected in localized increases in blood flow and tissue viability, all with minimal systemic effects. This technology can provide the basis for a timely treatment of a localized ischemia-associated disease to prevent injury in different tissues and organs.

Original languageEnglish (US)
Pages (from-to)2907-2919
Number of pages13
JournalACS Applied Bio Materials
Volume2
Issue number7
DOIs
StatePublished - May 27 2019

Fingerprint

S-Nitrosothiols
Nitric oxide
Magnetic Fields
Reperfusion Injury
Nanoparticles
Reperfusion
Nitric Oxide
Magnetic fields
Ischemia
Magnets
Leukocyte Rolling
Tissue
Tissue Survival
Peroxynitrous Acid
Arterial Pressure
Cell signaling
Technology
Reactive Nitrogen Species
Tourniquets
Venules

Keywords

  • ischemia/reperfusion
  • nanoparticles
  • nitric oxide
  • paramagnetic
  • peroxynitrite
  • S-nitrosothiols
  • targeted delivery

ASJC Scopus subject areas

  • Biomaterials
  • Chemistry(all)
  • Biomedical Engineering
  • Biochemistry, medical

Cite this

Reducing Ischemia/Reperfusion Injury by the Targeted Delivery of Nitric Oxide from Magnetic-Field-Induced Localization of S-Nitrosothiol-Coated Paramagnetic Nanoparticles. / Navati, Mahantesh S.; Lucas, Alfredo; Liong, Celine; Barros, Marcelo; Jayadeva, Jyothishree Tholalu; Friedman, Joel M.; Cabrales, Pedro.

In: ACS Applied Bio Materials, Vol. 2, No. 7, 27.05.2019, p. 2907-2919.

Research output: Contribution to journalArticle

Navati, Mahantesh S. ; Lucas, Alfredo ; Liong, Celine ; Barros, Marcelo ; Jayadeva, Jyothishree Tholalu ; Friedman, Joel M. ; Cabrales, Pedro. / Reducing Ischemia/Reperfusion Injury by the Targeted Delivery of Nitric Oxide from Magnetic-Field-Induced Localization of S-Nitrosothiol-Coated Paramagnetic Nanoparticles. In: ACS Applied Bio Materials. 2019 ; Vol. 2, No. 7. pp. 2907-2919.
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