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In this study, PIM1, a novel target predominantly expressed in macrophages during sepsis, is investigated by bioinformatics analysis and clinical evaluation in patients with sepsis compared with healthy individuals. The regulatory mechanism by which PIM1 promotes the release of tissue factors (TF) from macrophages by modulating the phosphorylation levels of mTOR through the AKT and MAPK signaling pathways is demonstrated both in vitro and in vivo. Based on these findings, a multifunctional co\u2010delivery system based on mesoporous polydopamine (MPDA) nanoparticles (NPs) coated with cationic polyethyleneimine (PEI) and macrophage\u2010targeting glucomannan (GM) (MPDA@PEI@GM NPs) is proposed for the co\u2010delivery of the PIM1 inhibitors SMI\u20104a and small interfering RNA (siPIM1) to downregulate PIM1 expression and improve sepsis\u2010induced coagulopathy. MPDA@SMI\u20104a@PEI\/siPIM1@GM demonstrates negligible cytotoxicity, excellent macrophage\u2010targeting efficiency, prolonged blood circulation, and significantly downregulated PIM1 expression. Notably, treatment with MPDA@SMI\u20104a@PEI\/siPIM1@GM improves the survival rates of septic mice by ameliorating disordered coagulation and alleviating lung injury. Bioinformatic analysis and clinical research\u2010guided MPDA@SMI\u20104a@PEI\/siPIM1@GM co\u2010delivery systems improve TF\u2010mediated coagulopathy in sepsis and alleviate sepsis\u2010induced acute lung injury, marking a significant advancement in the development of clinical antisepsis therapies.<\/jats:p>","DOI":"10.1002\/smll.202412688","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T01:40:49Z","timestamp":1743212449000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Multifunctional Co\u2010Delivery Systems with Downregulation of the Novel Target PIM1 in Macrophages to Ameliorate TF\u2010Mediated Coagulopathy in Sepsis"],"prefix":"10.1002","volume":"21","author":[{"given":"Aiming","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Intensive Care Unit The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang 32500 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