Steroid-loaded Avidin-Nucleic-Acid-Nano-Assemblies reduce hepatic fibrosis modulating Kupffer cells in primary biliary cholangitis
Year: 2026
Type: article
Abstract: Primary biliary cholangitis (PBC) is the most common life-long autoimmune liver disease arising from a biliary epithelial activation to a complex evolving cascade of immune-mediated injury, leading to inflammation and fibrosis and ultimately cirrhosis and liver failure. Ursodeoxycholic acid (UDCA) remains the only first-line treatment, despite being ineffective in approximately 40% of patients. Inadequate response to UDCA has been associated with increased death risk or need for liver transplantation. Starting from these premises, novel or repurposed drugs are currently needed. Immunosuppressive therapies, such as corticosteroids, remain controversial, primarily due to safety concerns related to off-target effects and limited evidence of enhanced efficacy. Nanoparticles are known to accumulate in the liver. Among them, Avidin-Nucleic-Acids-Nano-ASsemblies (ANANAS) have emerged as promising drug carriers thanks to their multi-functionality and convenient tunability, biodegradability, biocompatibility and scalable manufacturing. Despite the availability of numerous PBC models, none replicate key features of human disease to the degree observed in ARE Del-/- mice. Focusing on this model, ANANAS loaded with acid-releasable dexamethasone (ANANAS-Hz-Dex-M) were parenterally administered to evaluate distribution, pharmacokinetics, and therapeutic efficacy. The single treatment demonstrated selective liver tropism with an exclusive steroid release, and interaction with resident macrophages. Multiple administrations significantly reduced hepatic fibrosis. In vitro, isolated Kupffer cells from ARE Del-/- internalize the nanoassembly, with a reduction of the inflammatory profile. Our findings delineate ANANAS-Hz-Dex-M as a tool with the potential to guide resident macrophage plasticity and ameliorate disease course.
Source: Biomedicine & Pharmacotherapy
Authors: Martina Bruna Violatto, Manuela Vitulo, Elisa Schiavon, Chiara Caime, Annalisa Morelli, Martina Cattaneo, Naths Grazia Sukubo, Mara Corti, Giulia Yuri Moscatiello, Alessandro Enrico Galbussera, Alice Passoni, Alessia Lanno, Stefano Fumagalli, Davide Panzeri, Laura Sironi, Martina Stocco, Simone Bernardotto, Domenico Cerullo, Laura Cristoferi, Alessio Gerussi, Sara Pelucchi, Massimiliano Cadamuro, Marco Carbone, Pietro Invernizzi, Paolo Bigini, Margherita Morpurgo, Donatella Barisani
Language: English
Topic: Liver Diseases and Immunity
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,610
Funder: Ministero della Salute
Award: G420465300
OpenAlex ID: W7170101990