Yan, Ji-Jing Kim, Hyunjin Kim, Bomin Piao, Honglin Jang, Joon Young Kang, Tae Kyeom Lee, Wook-Bin Kim, Dohyeon Jo, Seunghyun Shin, Duckhyang Abuzar, Sharif M. D. Kim, Myung L. Yang, Jaeseok Jon, Sangyong 2025-03-22T12:30:35Z 2025-03-22T12:30:35Z 2025-03-19 2025-03 2192-2640 https://pubs.kist.re.kr/handle/201004/151992 Renal ischemia/reperfusion injury (IRI) is a common form of acute kidney injury. The basic mechanism underlying renal IRI is acute inflammation, where oxidative stress plays an important role. Although bilirubin exhibits potent reactive oxygen species (ROS)-scavenging properties, its clinical application is hindered by problems associated with solubility, stability, and toxicity. In this study, BX-001N, a synthetic polyethylene glycol-conjugated bilirubin 3 alpha nanoparticle is developed and assessed its renoprotective effects in renal IRI. Intravenous administration of BX-001N led to increase uptake in the kidneys with minimal migration to the brain after IRI. Peri-IRI BX-001N administration improves renal function and attenuates renal tissue injury and tubular apoptosis to a greater extent than free bilirubin on day 1 after IRI. BX-001N suppressed renal infiltration of inflammatory cells and reduced expression of TNF-alpha and MCP-1. Furthermore, BX-001N increases renal tubular regeneration on day 3 and suppresses renal fibrosis on day 28. BX-001N decreases the renal expressions of dihydroethidium, malondialdehyde, and nitrotyrosine after IRI. In conclusion, BX-001N, the first Good Manufacturing Practice-grade synthetic bilirubin-based nanomedicine attenuates acute renal injury and chronic fibrosis by suppressing ROS generation and inflammation after IRI. It shows adequate safety profiles and holds promise as a new therapy for renal IRI. English Wiley-Blackwell Synthetic Bilirubin-Based Nanomedicine Protects Against Renal Ischemia/Reperfusion Injury Through Antioxidant and Immune-Modulating Activity Article 10.1002/adhm.202403846 1 Advanced Healthcare Materials, v.14, no.7 Advanced Healthcare Materials 14 7 Y scie scopus 001402560400001 2-s2.0-85215702660 Engineering, Biomedical Nanoscience & Nanotechnology Materials Science, Biomaterials Engineering Science & Technology - Other Topics Materials Science Article ISCHEMIA-REPERFUSION INJURY OXIDATIVE STRESS KIDNEY-DISEASE NANOPARTICLE EXPRESSION ischemia/reperfusion injury kidney reactive oxygen species bilirubin nanoparticle immune modulation