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

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...

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Detalhes bibliográficos
Autores: Perramón Corominas, Meritxell, Navalón López, María, Fernández Varo, Guillermo, Moreno Lanceta, Alazne, García Pérez, Rocío, Faneca, Joana, López Moya, Mario, Fornaguera, Cristina, García Villoria, Judit, Morales Ruiz, Manuel, Melgar-Lesmes, Pedro, Borrós, Salvador, Jiménez Povedano, Wladimiro
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2024
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/222127
Acesso em linha:https://hdl.handle.net/2445/222127
Access Level:Acceso aberto
Palavra-chave:Hipertensió portal
Òxid nítric
Cirrosi hepàtica
Inflamació
Nanomedicina
Portal hypertension
Nitric oxide
Hepatic cirrhosis
Inflammation
Nanomedicine
Descrição
Resumo: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.

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