TY - JOUR
T1 - Polymeric nanoparticles for liver-targeted pituitary tumor-transforming gene 1 silencing in rats with chronic liver disease
AU - Perramón, Meritxell
AU - Navalón-López, María
AU - Fernández-Varo, Guillermo
AU - Casals, Gregori
AU - Faneca, Joana
AU - Macías-Herranz, Manuel
AU - Boix, Loreto
AU - Fundora, Yiliam
AU - Morales-Ruiz, Manuel
AU - García-Villoria, Judit
AU - Fornaguera, Cristina
AU - Borrós, Salvador
AU - Jiménez, Wladimiro
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/10
Y1 - 2025/10
N2 - Pituitary tumor transforming gene 1 (Pttg1) is upregulated in cirrhosis and hepatocarcinoma (HCC). We assessed the therapeutic effect of liver-targeted Pttg1 siRNA Retinol (Ret) pBAE nanoparticles (NPs) to treat these disturbances. Fibrosis was induced in Wistar rats by carbon tetrachloride inhalation and HCC by diethylnitrosamine injection. Ret pBAE NPs accumulated in hepatic tissue, close to zones positive for αSMA staining. Pttg1 interference increased mean arterial pressure, reduced portal hypertension and decreased collagen accumulation and inflammatory infiltrate in fibrotic rats. In HCC rats, Pttg1 silencing reduced liver to body weight ratio and hepatic proliferation and increased hepatic ATP production and serum glucose. This therapy effectively mitigated liver fibrosis and HCC progression in experimental models. The feasibility of this treatment was also demonstrated in human derived hepatic stellate cells and in ex vivo human cirrhotic livers underscoring the therapeutic potential of Pttg1 siRNA Ret pBAE NPs in addressing liver fibrosis and HCC.
AB - Pituitary tumor transforming gene 1 (Pttg1) is upregulated in cirrhosis and hepatocarcinoma (HCC). We assessed the therapeutic effect of liver-targeted Pttg1 siRNA Retinol (Ret) pBAE nanoparticles (NPs) to treat these disturbances. Fibrosis was induced in Wistar rats by carbon tetrachloride inhalation and HCC by diethylnitrosamine injection. Ret pBAE NPs accumulated in hepatic tissue, close to zones positive for αSMA staining. Pttg1 interference increased mean arterial pressure, reduced portal hypertension and decreased collagen accumulation and inflammatory infiltrate in fibrotic rats. In HCC rats, Pttg1 silencing reduced liver to body weight ratio and hepatic proliferation and increased hepatic ATP production and serum glucose. This therapy effectively mitigated liver fibrosis and HCC progression in experimental models. The feasibility of this treatment was also demonstrated in human derived hepatic stellate cells and in ex vivo human cirrhotic livers underscoring the therapeutic potential of Pttg1 siRNA Ret pBAE NPs in addressing liver fibrosis and HCC.
KW - Hepatocarcinoma
KW - Liver fibrosis
KW - Nanotherapies
KW - Poly(beta-amino ester) polymers
KW - Selective targeting
UR - https://www.scopus.com/pages/publications/105016785902
UR - http://hdl.handle.net/20.500.14342/5553
U2 - 10.1016/j.nano.2025.102860
DO - 10.1016/j.nano.2025.102860
M3 - Article
AN - SCOPUS:105016785902
SN - 1549-9634
VL - 69
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
M1 - 102860
ER -