Opsonized bilirubin nanomedicine targeting and repolarizing macrophage for acute lung injury treatment
Yinhao Lin1, Yanxian Hou1, Baiqun Duan2
1Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Background:
Acute lung injury (ALI) is a pathological condition characterized by diffuse lung injury. Excessive macrophage polarization to the M1 type in lung tissue plays a crucial role in the incidence and aggravation of ALI.
Research Design And Methods:
Bilirubin (BR) has been applied as a therapeutic agent in various diseases due to its ability to regulate macrophage polarization. Based on the inherent engulfing of M1 macrophages toward xenobiotic nanomedicines, an inhalable BR nanomedicine was developed for the treatment of ALI. The BR nanoparticles (BRn) were first prepared using a one-step nanoprecipitation method, followed by surface modification with immunoglobulin G (IgG) at a 20% weight ratio to prepare BRn@IgG.
Results:
Both nanoparticles exhibited excellent stability and enhanced antioxidative properties in aqueous phases. To gain the initiative, the IgG-modified nanoparticles could smartly bind to M1 macrophages, resulting in greatly improved BR delivery efficiency to macrophages and thus enhancing antioxidative, anti-inflammatory, and polarization-regulating effects compared to naked BRn. BRn@IgG evaded mechanical clearance from lung tissue and demonstrated prolonged retention in the pulmonary environment, thereby attaining the most potent therapeutic effect among all formulations in this study.
Conclusion:
BRn@IgG could be considered a novel and effective therapeutic agent for the ALI treatment.
