Armillotta MG, Lizzi L, Massimi M. Nanoparticle-based systems for liver therapy: Overcoming fibrosis and enhancing drug efficacy. World J Hepatol 2025; 17(10): 108810 [DOI: 10.4254/wjh.v17.i10.108810]
Corresponding Author of This Article
Mara Massimi, PhD, Associate Professor, Department of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, L'Aquila 67100, AQ, Italy. mara.massimi@univaq.it
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Gastroenterology & Hepatology
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Review
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Oct 27, 2025 (publication date) through Oct 28, 2025
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World Journal of Hepatology
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1948-5182
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Armillotta MG, Lizzi L, Massimi M. Nanoparticle-based systems for liver therapy: Overcoming fibrosis and enhancing drug efficacy. World J Hepatol 2025; 17(10): 108810 [DOI: 10.4254/wjh.v17.i10.108810]
World J Hepatol. Oct 27, 2025; 17(10): 108810 Published online Oct 27, 2025. doi: 10.4254/wjh.v17.i10.108810
Nanoparticle-based systems for liver therapy: Overcoming fibrosis and enhancing drug efficacy
Maria Giovanna Armillotta, Lara Lizzi, Mara Massimi
Maria Giovanna Armillotta, Department of Clinical and Experimental Medicine, University of Foggia, Foggia 71121, FG, Italy
Lara Lizzi, Mara Massimi, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila 67100, AQ, Italy
Co-first authors: Maria Giovanna Armillotta and Lara Lizzi.
Author contributions: Armillotta MG, Lizzi L, and Massimi M were responsible for the conceptualization of the study; Armillotta MG and Lizzi L were responsible for writing the original draft of the manuscript; Lizzi L and Massimi M were responsible for reviewing and editing the paper; Lizzi L was responsible for preparing the tables and images; All authors reviewed the paper and agreed to the published version of the manuscript. Armillotta MG and Lizzi L contributed equally to this study as co-first authors.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mara Massimi, PhD, Associate Professor, Department of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, L'Aquila 67100, AQ, Italy. mara.massimi@univaq.it
Received: April 24, 2025 Revised: June 17, 2025 Accepted: August 25, 2025 Published online: October 27, 2025 Processing time: 187 Days and 0.3 Hours
Abstract
Liver diseases are among the most insidious and life-threatening conditions due to their progressive nature and late symptom onset. Cirrhosis and hepatocellular carcinoma account for most liver-related deaths, often following the progression from fibrosis. Fibrosis creates a hostile microenvironment, characterized by portal hypertension, vascular capillarization, intrahepatic vasoconstriction, and extracellular matrix deposition, which severely limits drug efficacy. Advances in pharmaceutical science have prompted efforts to develop liver-targeted drug delivery systems to prevent or reduce the progression of fibrosis, a central feature of many liver diseases. Fibrosis often reduces the in vivo efficacy of both approved and experimental drugs, underscoring the need for improved delivery strategies focused on stability, controlled release, and precise targeting. Nanoparticle (NP)-based systems show promise, either by delivering therapeutic agents, or in some cases, by contributing directly to the therapeutic effects. This review summarizes the main types of NPs explored for liver disease treatment, especially those aiming to reverse fibrosis or prevent its progression, a critical therapeutic target in chronic liver diseases. Additionally, it examines gene delivery and ultrasound-guided microbubble strategies, which can be combined with NPs to improve cell-specific targeting and boost therapeutic effects. Together, these approaches have the potential to address current therapeutic challenges and accelerate the development of liver-targeted treatments for clinical application.
Core Tip: Liver diseases, including fibrosis and hepatocellular carcinoma, represent major global health challenges with limited treatment options, partly due to drug delivery barriers. Therapeutic efficacy is hindered by factors such as portal hypertension, vascular alterations, and particularly the fibrotic microenvironment. This review summarizes the latest advances in nanoparticle (NP)-based delivery strategies targeting liver fibrosis, focusing on lipid-based, polymeric, and inorganic NPs. It also explores emerging combinatorial technologies including gene delivery platforms and ultrasound-assisted microbubble systems. Finally, it briefly integrates toxicity issues, translational considerations, and artificial intelligence-guided NPs to provide a comprehensive yet focused overview of promising therapeutic avenues.
