Adaptive bilirubin nanoscavenger alleviates pulmonary oxidative stress and inflammation for acute lung injury therapy

作者：Longfa Kou, Yitianhe Xu, Shize Li, Zhinan He, Di Huang, Zhanzheng Ye, Yixuan Zhu, Yunzhi Wang, Xinyu Di, Yuqi Yan, Yinhao Lin, Wanling Zhu, Xianbao Shi, Hailin Zhang, Ruijie Chen · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.03.027 · 被引用次数：22 · 研究领域：Heme Oxygenase-1 and Carbon Monoxide、Neonatal Health and Biochemistry、Hemoglobin structure and function

INTRODUCTION: Acute lung injury (ALI) is a life-threatening condition characterized by rapidly progressing respiratory distress and hypoxemia. Oxidative stress-induced inflammation in lung tissue plays a crucial role in the progression of ALI. Excessive generation of reactive oxygen species (ROS) in the pulmonary microenvironment activates inflammatory signaling pathways, enhancing the transcription of pro-inflammatory factors and ultimately leading to tissue necrosis. OBJECTIVES: Bilirubin (BR), an exceptional endogenous antioxidant, possesses the ability to counteract elevated levels of reactive oxygen species (ROS) through direct reactions or by inducing antioxidant systems such as Nrf2/HO-1 signaling. However, its limited solubility poses a hindrance to further applications. Hence, it is imperative to develop a suitable bilirubin-based system for biological utilization. METHODS: In this study, we developed a bilirubin-based ROS-sensitive adaptive nanoscavenger (GP@BR) by co-assembling bilirubin-conjugated glycol chitosan (GC-BR) and bilirubin-conjugated polyethylene glycol (PEG-BR), aiming to alleviate oxidative stress for ALI treatment. RESULTS: The different conjugations endowed the bilirubin derivatives with varying sensitivity towards reacting with ROS, enabling GP@BR to exert antioxidative properties specifically in oxidative environments on demand. Besides its excellent antioxidant properties, GP@BR also demonstrated the ability to absorb excess inflammatory cytokin...