@article{2a52eecec39b41d9b024bd2f0f27e6d2,
title = "Dually Active Polycation/miRNA Nanoparticles for the Treatment of Fibrosis in Alcohol-Associated Liver Disease",
abstract = "Alcohol-associated liver disease (AALD) is a major cause of liver disorders worldwide. Current treatment options are limited, especially for AALD-associated fibrosis. Promising approaches in-clude RNA interference for miR-155 overexpression in Kupffer cells (KCs), as well as the use of CXCR4 antagonists that inhibit the activation of hepatic stellate cells (HSCs) through the CXCL12/CXCR4 axis. The development of dual-functioning nanoparticles for the effective delivery of antifibrotic RNA together with a CXCR4 inhibitor thus promises to improve the treatment of AALD fibrosis. In this study, cholesterol-modified polymeric CXCR4 inhibitor (Chol-PCX) was synthesized and used to encapsulate anti-miR-155 or non-coding (NC) miRNA in the form of Chol-PCX/miRNA nanoparticles. The results indicate that the nanoparticles induce a significant miR-155 silencing effect both in vitro and in vivo. Treatment with the Chol-PCX/anti-miR-155 particles in a model of moderate alcohol consumption with secondary liver insult resulted in a significant reduction in aminotransferase enzymes as well as collagen content in the liver parenchyma. Overall, our data support the use of Chol-PCX as a carrier for anti-miR-155 for the combined therapeutic inhibition of CXCR4 and miR-155 expression as a way to improve fibrotic damage in the liver.",
keywords = "CXCR4, alcohol-associated liver disease (AALD), miR-155, nanoparticles",
author = "Chuhan Zhang and Yu Hang and Weimin Tang and Diptesh Sil and Jensen-Smith, {Heather C.} and Bennett, {Robert G.} and McVicker, {Benita L.} and David Oupick{\'y}",
note = "Funding Information: Funding: This work was supported by the NIH grant R01 AA027695 (D.O.) and by the Department of Veterans Affairs BLR&D grants I01 BX004127 (B.L.M.) and I01 BX000849 (R.G.B.). The authors acknowledge the Multiphoton Intravital and Tissue Imaging Core (MITI) which receives support through the Nebraska Center for Nanomedicine and the Cognitive Neuroscience of Development & Aging Centers for Biomedical Research Excellence (NIH P30 GM127200, P20 GM130447), Fred and Pamela Buffett Cancer Center (NIH P30 CA036727), state funds from the Nebraska Research Initiative, and institutionally by the UNMC Office of the Vice Chancellor for Research. The UNMC Advanced Microscopy Core Facility receives partial support from the National Institute for General Medical Science (NIGMS) INBRE-P20 GM103427 and COBRE-P30 GM106397 grants, as well as support from the National Cancer Institute (NCI) for The Fred & Pamela Buffett Cancer Center Support Grant-P30 CA036727, and the Nebraska Research Initiative. This publication{\textquoteright}s contents and interpretations are the sole responsibility of the authors. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2022",
month = mar,
doi = "10.3390/pharmaceutics14030669",
language = "English (US)",
volume = "14",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "3",
}