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The complexity of multiple interrelated pathways involved in this process makes it challenging for monotherapy to achieve the desired therapeutic effects. To address this issue, this study designs a ROS\u2010activated heterodimer conjugate (VTO) to collaboratively alleviate LF. Additionally, a biomimetic high\u2010density lipoprotein is utilized for encapsulation, resulting in the formation of PL\u2010VTO, which enables natural liver targeting. Once PL\u2010VTO is delivered to the fibrotic liver, it can respond and release both parent drugs upon encountering the high ROS microenvironment, effectively scavenge ROS, induce quiescence of activated HSCs, and reduce collagen deposition, ultimately reversing LF. Overall, this study presents a feasible and versatile nanotherapeutic approach to enhance the prodrug\u2010driven treatment of LF.<\/jats:p>","DOI":"10.1002\/smtd.202402247","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T03:52:13Z","timestamp":1742356333000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Engineered Intelligent Microenvironment Responsive Prodrug Conjugates Navigated by Bioinspired Lipoproteins for Reversing Liver Fibrosis"],"prefix":"10.1002","volume":"9","author":[{"given":"Mingzhu","family":"Fang","sequence":"first","affiliation":[{"name":"Key Laboratory of Smart Drug Delivery (Ministry of Education) Minhang Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science School of Pharmacy Fudan University  Shanghai 201203 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