Polymeric nanoparticles for liver-targeted pituitary tumor-transforming gene 1 silencing in rats with chronic liver disease
Year: 2025
Type: article
Abstract: 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. Retinol (Ret) poly(beta-amino ester) (pBAE) nanoparticles (NPs) containing Pttg1 small interfering RNA (siRNA) specifically target the liver. These NPs effectively mitigate liver fibrosis and tumor progression in CCl 4 -induced fibrosis and diethylnitrosamine (DEN)-induced hepatocarcinoma rats, respectively. The feasibility of the treatment was also demonstrated in human-derived hepatic stellate cells and precision cut liver slices of human cirrhotic livers. These results unveil the therapeutic potential of Pttg1 siRNA Ret pBAE NPs in the treatment of chronic liver disease. • Pttg1 siRNA Retinol (Ret) pBAE nanoparticles (NPs) selectively target the liver. • These NPs reduce fibrosis and HCC progression in rats with fibrosis or HCC. • These NPs inhibit Pttg1 mRNA in LX2 cells and human precision cut liver slices. • Pttg1 siRNA Ret pBAE NPs have therapeutic potential in chronic liver disease.
Institutions: Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Institut Químic de Sarrià, Universitat Ramon Llull, Universitat de Barcelona, Instituto de Salud Carlos III, Centre for Biomedical Network Research on Rare Diseases, Institució Catalana de Recerca i Estudis Avançats
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,670
OpenAlex ID: W4414498146