Liver-targeted nanoparticles delivering nitric oxide reduce portal hypertension in cirrhotic rats

Meritxell Perramón, María Navalón-López, Guillermo Fernández-Varo, Alazne Moreno-Lanceta, Rocío García-Pérez, Joana Faneca, Mario López-Moya, Cristina Fornaguera, Judith García-Villoria, Manuel Morales-Ruiz, Pedro Melgar-Lesmes, Salvador Borrós, Wladimiro Jiménez

Research output: Indexed journal article Articlepeer-review

Abstract

Nitric oxide (NO) is a small vasodilator playing a key role in the pathogenesis of portal hypertension. Here, we assessed the potential therapeutic effect of a NO donor targeted to the liver by poly(beta-amino ester) nanoparticles (pBAE NPs) in experimental cirrhosis. Retinol-functionalized NO donor pBAE NPs (Ret pBAE NPs) were synthetized with the aim of actively targeting the liver. Administration of Ret pBAE NPs resulted in uptake and transfection by the liver and spleen. NPs were not found in other organs or the systemic circulation. Treatment with NO donor Ret pBAE NPs (30 mg/ kg body weight) significantly decreased aspartate aminotransferase, lactate dehydrogenase and portal pressure (9.75 ± 0.64 mmHg) compared to control NPs (13.4 ± 0.53 mmHg) in cirrhotic rats. There were no effects on mean arterial pressure and cardiac output. Liver-targeted NO donor NPs reduced collagen fibers and steatosis, activation of hepatic stellate cells and mRNA expression of profibrogenic and proinflammatory genes. Finally, Ret pBAE NPs displayed efficient transfection in human liver slices. Overall, liver-specific NO donor NPs effectively target the liver and mitigated inflammation and portal hypertension in cirrhotic rats. The use of Ret pBAE may prove to be an effective therapeutic strategy to treat advanced liver disease.

Original languageEnglish
Article number116143
JournalBiomedicine and Pharmacotherapy
Volume171
DOIs
Publication statusPublished - Feb 2024

Keywords

  • Inflammation
  • Liver cirrhosis
  • Nanomedicine
  • Nitric oxide donor
  • Portal pressure

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