{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:42:51Z","timestamp":1790390571848,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82002101"],"award-info":[{"award-number":["82002101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82002096"],"award-info":[{"award-number":["82002096"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015640","name":"Tongji Hospital","doi-asserted-by":"publisher","award":["2023A15"],"award-info":[{"award-number":["2023A15"]}],"id":[{"id":"10.13039\/501100015640","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis\u2010induced myopathy (SIM) is a severe complication that contributes to late\u2010stage mortality and functional impairment in sepsis patients. The NLRP3 inflammasome plays a pivotal role in the pathogenesis of SIM, and its selective inhibitor MCC950 has shown promising therapeutic potential. However, systemic administration of MCC950 is limited by hepatotoxicity, necessitating the development of targeted delivery systems to enhance efficacy while minimizing toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To improve the therapeutic profile of MCC950, we designed M12\u2010functionalized liposomal nanoparticles (M12\u2010Liposome@MCC950 NPs) as the carrier material, with surface modification by the muscle\u2010homing peptide M12 for targeted delivery to skeletal muscle tissue. Nanoparticle characteristics were assessed using transmission electron microscopy (TEM), dynamic light scattering (DLS) and in\u00a0vitro drug release assays. The targeting efficiency was evaluated in\u00a0vivo using fluorescence imaging and in\u00a0vitro via cellular uptake studies in C2C12 myoblasts. The anti\u2010inflammatory and anti\u2010atrophic effects were investigated in an LPS\u2010induced myotube atrophy model and a cecal ligation and puncture (CLP)\u2010induced sepsis mouse model. Biocompatibility and systemic safety were assessed through histological analysis and serum biochemical assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>M12\u2010Liposome@MCC950 NPs exhibited a uniform spherical morphology, an average diameter of 150\u2009\u00b1\u200910\u2009nm and a zeta potential of \u221215.73\u2009\u00b1\u20096.03\u2009mV, ensuring good colloidal stability. The nanoparticles demonstrated sustained drug release over 14\u2009days. In\u00a0vivo fluorescence imaging confirmed enhanced skeletal muscle accumulation of M12\u2010conjugated nanoparticles, with a 3.47\u2010 to 5.31\u2010fold increase compared to nontargeted controls. Cellular uptake studies revealed a 2.28\u2010fold improvement in intracellular delivery efficiency. In\u00a0vitro, M12\u2010Liposome@MCC950 NPs significantly inhibited NLRP3 inflammasome activation, reducing caspase\u20101 cleavage and IL\u20101\u03b2\/IL\u201018 secretion, while also preventing LPS\u2010induced myotube atrophy. In the CLP\u2010induced sepsis model, treatment with M12\u2010Liposome@MCC950 NPs markedly reduced muscle atrophy, improved grip strength and decreased expression of atrophy\u2010related proteins Atrogin\u20101 and MuRF1. Additionally, histological and biochemical assessments confirmed that the nanoparticles did not induce hepatic or renal toxicity, demonstrating excellent biocompatibility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>M12\u2010Liposome@MCC950 NPs provide a targeted and sustained\u2010release strategy for delivering MCC950 to skeletal muscle, effectively inhibiting NLRP3 inflammasome activation and alleviating SIM. This approach enhances therapeutic efficacy while mitigating systemic toxicity, highlighting the potential of nanomedicine\u2010based interventions for treating inflammation\u2010related myopathies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70285","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T10:45:59Z","timestamp":1776249959000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["MCC950\u2010Loaded M12\u2010Liposome Nanoparticles for Targeted Inhibition of NLRP3 Inflammasome in Sepsis\u2010Induced Muscle Atrophy"],"prefix":"10.1002","volume":"17","author":[{"given":"Yukun","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Plastic and Aesthetic Surgery, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan 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