{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T13:34:15Z","timestamp":1792503255929,"version":"4.5.0"},"reference-count":34,"publisher":"American Association for the Advancement of Science (AAAS)","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82474244"],"award-info":[{"award-number":["No. 82474244"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Liaoning Provincial Department of Education for Universities"},{"name":"Liaoning Province Joint Science and Technology Program","award":["2024-BSLH-051"],"award-info":[{"award-number":["2024-BSLH-051"]}]},{"name":"Liaoning Provincial Department of Science and Technology Applied Basic Research Program Project","award":["2023JH2\/101300101"],"award-info":[{"award-number":["2023JH2\/101300101"]}]}],"content-domain":{"domain":["spj.science.org"],"crossmark-restriction":true},"short-container-title":["Biomater Res"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>M1-like macrophages dominate local and systemic inflammatory response progression in acute pancreatitis (AP). The development of strategies to target pro-inflammatory M1-like macrophages in conjunction with primary pathophysiology-specific pharmacological therapy presents a challenge in the management of AP. Peptide\u2013drug conjugates (PDCs), which are emerging second-generation conjugate drugs, have quickly become a new favorite in the field of targeted drug delivery due to their superior drug bioavailability, affinity, and stability. Tasquinimod (Tasq) is a specific inhibitor of S100A9 that is expressed mainly in M1-like macrophages during AP. Drug repositioning revealed that Tasq improved AP in a dose-dependent manner, but drug toxicity occurred at doses of 30 mg\/kg. Therefore, we selected 2 specific M1-like macrophage-binding peptides (M1peps) by phage display technology and developed a novel PDC, M1pep-Tasq, by connecting M1peps to activated Tasq with a cleavable linker. Based on a mouse model of AP constructed by retrograde injection of sodium taurine cholate into the bile pancreatic duct and an M1-like macrophage polarization model induced by lipopolysaccharide + interferon-\u03b3 stimulation, we confirmed that M1pep-Tasq reduces the drug toxicity of Tasq and improves its efficacy by enhancing the targeting of Tasq to damaged organs in\u00a0vivo and to M1-like macrophages in\u00a0vitro. Furthermore, M1pep-Tasq effectively improves AP by inhibiting M1-like macrophage polarization by suppressing the S100A9\u2013TLR4\u2013MAPK pathway. Overall, we have developed a novel PDC, M1pep-Tasq, with promising applications in clinical settings to treat a range of inflammatory disorders by increasing the efficacy and reducing the toxicity of Tasq.<\/jats:p>","DOI":"10.34133\/bmr.0250","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T16:55:33Z","timestamp":1755795333000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":3,"title":["The Peptide\u2013Drug Conjugate M1pep\u2013Tasquinimod Ameliorates Acute Pancreatitis via Selectively Clearing M1-like Macrophages"],"prefix":"10.34133","volume":"29","author":[{"given":"Fangyue","family":"Guo","sequence":"first","affiliation":[{"name":"Laboratory of Integrative Medicine, \rFirst Affiliated Hospital of Dalian Medical University, Dalian 116011, 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