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Copyright: ©Author(s) 2027. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Gastroenterol. Jan 7, 2027; 33(1): 123681
Published online Jan 7, 2027. doi: 10.3748/wjg.123681
Small extracellular vesicles as liquid biopsy targets and precision therapeutics for metabolic dysfunction-associated steatotic liver disease
Ling-Ling Ding, Han Liu, Yang Yu, Xue-Chao Liu, Shu-Qin Zhang, Hui Qian, Dong-Lin Hao
Ling-Ling Ding, Han Liu, Dong-Lin Hao, Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213002, Jiangsu Province, China
Ling-Ling Ding, Han Liu, Xue-Chao Liu, Shu-Qin Zhang, Department of Basic Medical Sciences, School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu Province, China
Yang Yu, Hui Qian, Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu Province, China
Co-corresponding authors: Ling-Ling Ding and Dong-Lin Hao.
Author contributions: Ding LL, Qian H, and Hao DL were responsible for the conceptual framework of this review and the final review of the manuscript; Ding LL and Hao DL contributed equally to this manuscript as co-corresponding authors; Ding LL, Liu H, Yu Y, Liu XC, and Zhang SQ were responsible for drafting the manuscript; Ding LL, Liu H, and Yu Y were involved in the critical review and revision of the manuscript, and prepared the figures and tables. All authors have read and approved the final version of the manuscript.
AI contribution statement: ChatGPT (GPT-5.6 Sol, OpenAI) was used to a limited extent during manuscript preparation and revision for language polishing and editorial assistance, including grammar correction, wording refinement, and improvement of clarity and readability. The substantive scientific content and the majority of the manuscript were developed by the authors. Final decisions regarding literature selection, evidence evaluation, scientific interpretation, and conclusions were made and verified by the authors. AI tools were not used to generate research data or perform statistical analyses. All AI-assisted text was critically reviewed, verified against the original literature where applicable, and appropriately revised by the authors. The authors take full responsibility for the accuracy, originality, scientific content, and integrity of the final manuscript.
Supported by the High-Level Talent Scientific Research Start-up Funding of Jiangsu University, No. 5501280008; Jiangsu Province Double Innovation Doctoral Talent Program, No. JSSCBS20221179; the China Postdoctoral Science Foundation, No. 2023M741425; and the Industry-University-Research Cooperation Project with Nanjing EVLiXiR, No. 8411283025.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Ling-Ling Ding, Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, No. 2 Yongning North Road, Changzhou 213002, Jiangsu Province, China. l.ding@ujs.edu.cn
Received: May 26, 2026
Revised: August 13, 2026
Accepted: October 8, 2026
Published online: January 7, 2027
Processing time: 167 Days and 16.6 Hours
Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over one-third of the global population, yet robust molecular biomarkers for early disease activity and treatment monitoring remain limited. Small extracellular vesicles (sEVs) carry nucleic acids, proteins, and lipids that reflect disease-associated intercellular signaling and are being investigated as liquid-biopsy analytes and therapeutic platforms. Candidate sEV miRNAs, proteins, and lipid signatures have shown potential for disease characterization, but evidence derives mainly from small, heterogeneous cohorts with limited external validation. No sEV-based assay is established for routine MASLD diagnosis, staging, or treatment monitoring. Mesenchymal stem cell-derived sEVs and engineered sEV platforms have shown therapeutic potential in preclinical MASLD-related models through modulation of inflammation, oxidative stress, lipid metabolism, and targeted cargo delivery, although some engineering strategies remain supported primarily by non-MASLD proof-of-concept evidence. Key barriers to translation include heterogeneity in extracellular vesicle isolation and characterization, lipoprotein co-isolation, prospective multicenter validation, and, for therapeutic products, manufacturing consistency, biodistribution, dosing, and safety. This narrative review integrates diagnostic and therapeutic evidence within an evidence-classified translational framework.

Keywords: Metabolic dysfunction-associated steatotic liver disease; Small extracellular vesicles; Extracellular vesicles; Liquid biopsy; Biomarkers; Noninvasive tests; Drug delivery systems; Therapeutic strategies

Core Tip: Metabolic dysfunction-associated steatotic liver disease (MASLD) lacks non-invasive biomarkers and targeted therapies. Small extracellular vesicles (sEVs) offer dual solutions: As diagnostic tools, sEV-derived miRNAs (e.g., miR-122), proteins (e.g., Kelch-like protein 41), and lipids enable accurate staging; as therapeutics, mesenchymal stem cell-derived sEVs reduce steatosis and fibrosis via autophagy and oxidative stress regulation, while engineered sEVs (e.g., cyclic arginine-glycine-aspartic acid-modified) enhance targeted delivery. sEVs thus shift from bystanders to key diagnostic and therapeutic players in MASLD.

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