| Autor: |
Panzarini E; Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, 73100 Lecce, Italy., Leporatti S; Consiglio Nazionale delle Ricerche (CNR) NANOTEC istituto di Nanotecnologia-Istituto di Nanotecnologia, 73100 Lecce, Italy., Tenuzzo BA; Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, 73100 Lecce, Italy., Quarta A; Consiglio Nazionale delle Ricerche (CNR) NANOTEC istituto di Nanotecnologia-Istituto di Nanotecnologia, 73100 Lecce, Italy., Hanafy NAN; Nanomedicine Department, Institute of Nanoscience and Nanotechnology, Kafrelsheikh University, Kafr El Sheikh 6860404, Egypt., Giannelli G; National Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy, Moliterni C; Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, 00185 Rome, Italy., Vardanyan D; Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, 73100 Lecce, Italy., Sbarigia C; Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, 00185 Rome, Italy., Fidaleo M; Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, 00185 Rome, Italy.; Research Center for Nanotechnology for Engineering of Sapienza (CNIS), Sapienza University of Rome, 00185 Rome, Italy., Tacconi S; Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, 00185 Rome, Italy., Dini L; Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, 00185 Rome, Italy.; Research Center for Nanotechnology for Engineering of Sapienza (CNIS), Sapienza University of Rome, 00185 Rome, Italy. |
| Abstrakt: |
Hepatic fibrosis (HF) is a major cause of liver-related disorders and together with cancer-associated fibroblasts can favor liver cancer development by modulating the tumor microenvironment. Advanced HF, characterized by an excess of extracellular matrix (ECM), is mediated by TGF- β1, that activates hepatic stellate cells (HSCs) and fibroblasts. A TGF-β1 receptor inhibitor, LY2157299 or Galunisertib (GLY), has shown promising results against chronic liver progression in animal models, and we show that it can be further improved by enhancing GLYs bioavailability through encapsulation in polymeric polygalacturonic-polyacrylic acid nanomicelles (GLY-NMs). GLY-NMs reduced HF in an in vivo rat model of liver fibrosis induced by intraperitoneal injection of CCl 4 as shown by the morphological, biochemical, and molecular biology parameters of normal and fibrotic livers. Moreover, GLY-NM was able to induce recovery from HF better than free GLY. Indeed, the encapsulated drug reduces collagen deposition, hepatic stellate cells (HSCs) activation, prevents fatty degeneration and restores the correct lobular architecture of the liver as well as normalizes the serum parameters and expression of the genes involved in the onset of HF. In summary, GLY-NM improved the pharmacological activity of the free TGF- β1 inhibitor in the in vivo HF treatment and thus is a candidate as a novel therapeutic strategy. |
