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To address this multifactorial pathology, we developed an integrated nano\u2010therapeutic platform, termed CMEPA, that unites three complementary components: a copper\u2010based nanozyme with dual superoxide dismutase (SOD)\u2010 and catalase (CAT)\u2010like activities, human umbilical cord mesenchymal stem cell\u2010derived exosomes (UC\u2010MSC\u2010Exos) enriched in regulatory microRNAs, and a hepatocyte\u2010targeting antibody against ASGR1. In vitro, CMEPA efficiently scavenged reactive oxygen species (ROS), significantly reduced lipid droplet accumulation, and suppressed apoptosis in palmitic acid\u2010challenged hepatocytes. In vivo, CMEPA exhibited preferential hepatic accumulation and an excellent biosafety profile, with no observable systemic toxicity. Therapeutic evaluation in a diet\u2010induced murine MASLD model revealed that CMEPA administration significantly improved serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride, and cholesterol levels, alleviated hepatic steatosis as confirmed by histopathology, enhanced endogenous SOD and CAT activities, and attenuated inflammatory and lipogenic signaling pathways, as revealed by transcriptomic analysis. Collectively, these results establish CMEPA as a robust, multi\u2010modal nano\u2010therapeutic strategy that integrates catalytic antioxidation, exosome\u2010mediated gene regulation, and active hepatocyte targeting, offering a promising translational approach for MASLD treatment.<\/jats:p>","DOI":"10.1002\/adhm.71147","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:21:11Z","timestamp":1776057671000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An Integrated Nanozyme\u2010Exosome Platform for Multi\u2010Targeted Therapy of Metabolic\u2010Associated Steatotic Liver Disease"],"prefix":"10.1002","volume":"15","author":[{"given":"Kun","family":"Yu","sequence":"first","affiliation":[{"name":"Lianyungang Second People's Hospital Affiliated to Kangda College of Nanjing Medical University  Lianyungang P. R. 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