Liver-targeted nanoparticles delivering nitric oxide reduce portal hypertension in cirrhotic rats - 04/02/24
, María Navalón-López c, Guillermo Fernández-Varo a, b, Alazne Moreno-Lanceta a, f, Rocío García-Pérez d, Joana Faneca a, Mario López-Moya c, Cristina Fornaguera c, Judith García-Villoria a, e, Manuel Morales-Ruiz a, b, f, Pedro Melgar-Lesmes a, b, f, g, Salvador Borrós c, Wladimiro Jiménez a, b, fAbstract |
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.
El texto completo de este artículo está disponible en PDF.Highlights |
• | Ret pBAE NPs containing a NO donor selectively target the liver in cirrhotic rats. |
• | NO Ret pBAE NPs decrease portal pressure and do not modify MAP in cirrhotic rats. |
• | Hepatic delivery of NO by Ret pBAE NPs ameliorates inflammation and fibrogenesis. |
• | NO delivery using Ret pBAE NPs is a new approach to manage portal hypertension. |
Abbreviations : AA, αSMA, CO, CT, Cy5, DAPI, ECM, Et-1, H NMR, HSC, hPCLS, IL, i.v., LD, MAP, NO, NOS, NPs, pBAE, PDI, PP, Ptgs2, Ret, Timp, Tnfα,, TPR
Keywords : Nanomedicine, Liver cirrhosis, Portal pressure, Inflammation, Nitric oxide donor
Esquema
Vol 171
Artículo 116143- février 2024 Regresar al número
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