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Therefore, targeted inhibiting the activation of HSCs induced by mechanical traction is the main measure to improve liver fibrosis. The activated HSCs (aHSCs)-targeted drug delivery nanosystem of verteporfin@polyethyleneimine-vitamin A (VP@PSA), which loaded VP a small molecule inhibitor of YAP in the Hippo signaling pathway to regulate mechanical signal transduction was constructed. The particle size of VP@PSA was 167.1 \u00b1 1.5 nm with great stability, and the drug loading of VP was 34.39 \u00b1 2.41% and encapsulation efficiency was 93.28 \u00b1 1.57%. The targeting and therapeutic effect of VP@PSA were verified by immunofluorescence, flow cytometry and competitive inhibition experiments. The biocompatibility was evaluated by hemolysis, pyrogen, vascular stimulation, respiration and behavior. Compared with non-targeted delivery system, VP@PSA showed best targeting ability to aHSCs among different kinds of liver cells. VP@PSA had an excellent therapeutic effect on suppressing the activation of HSCs, reducing ECM deposition and improving liver fibrosis by regulating YAP\/ lysyl oxidase like 2\/connective tissue growth factor signal\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Furthermore, VP@PSA had favorable biological safety and no toxicity to the main organs. The constructed VP@PSA delivery system laid a solid theoretical and experimental foundation for developing clinical targeted drugs for liver fibrosis.\n                  <\/jats:p>","DOI":"10.1088\/1361-6528\/ae6788","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T22:48:07Z","timestamp":1777675687000},"page":"205101","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Construction of hepatic stellate cells-targeted nanosystem of verteporfin for the effective treatment of liver fibrosis through mechanical signal modulation"],"prefix":"10.1088","volume":"37","author":[{"given":"Qian-Qian","family":"Ma","sequence":"first","affiliation":[{"name":"School of Pharmacy, Fourth Military Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Fourth Military Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Si-Yuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Fourth Military Medical University"},{"name":"Key Laboratory of Gastrointestinal Pharmacology of the State Administration of Traditional Chinese Medicine, Fourth Military Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9008-5391","authenticated-orcid":true,"given":"Bang-Le","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Fourth Military Medical University"},{"name":"Key Laboratory of Gastrointestinal Pharmacology of the State Administration of Traditional Chinese Medicine, Fourth Military Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7664-4716","authenticated-orcid":true,"given":"Li- Shuang","family":"Hou","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Fourth Military Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"266","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"nanoae6788bib1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2026.173910","type":"journal-article","article-title":"Decoupling multicellular activation circuits: MPDA-mediated co-delivery of quercetin\/simvastatin for potent hepatic fibrosis reversal","volume":"531","author":"Zhang","year":"2026","journal-title":"Chem. 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