Bilirubin Nanoparticles Alleviate Sepsis-Induced Acute Lung Injury by Protecting Pulmonary Endothelia Glycocalyx and Reducing Inflammation

Acute lung injury (ALI) remains one of the most common complications of sepsis. Although many potential effective pharmacologic and ventilatory treatment strategies have been reported, there is still a lack of effective means of treatment of sepsis-induced ALI in the clinic. The aim of this study is to develop an easy-made endogenous bilirubin nanoparticle (BRNP) that could treat sepsis-induced ALI and investigate its underlying therapeutic mechanism. We prepared BRNP by bilirubin (BR) self-assembly and bovine serum albumin (BSA) coating with a simple one-pot nanoprecipitation method. BRNP holds good physical stability and could release BR in a sustained manner in a neutral medium but initiate a burst release in either acidic or oxidative conditions. In a sepsis murine model, BRNP could substantially alleviate the sepsis-induced lung injury, as evidenced by reduced histopathological changes of lung tissues and also reduced inflammation development. Mechanically, BRNP could alleviate the glycocalyx damage, inhibit the NF-κB pathway, and reduce proinflammatory factor release in vivo. This study provides a simple and robust BRNP to treat sepsis-induced ALI, which may pave the way to design multifunctional nanomedicine for clinical translation.