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Bilirubin nanomedicines for the treatment of reactive oxygen species (ROS)-mediated diseases.

Reactive oxygen species (ROS) are chemically reactive species that are produced in cellular aerobic metabolism. They mainly include superoxide anion, hydrogen peroxide, hydroxyl radicals, singlet oxygen, ozone and nitric oxide, and are implicated in many physiological and pathological processes. Bilirubin, a cardinal pigment in the bile, has been increasingly investigated to treat cancer, diabetes, ischemia/reperfusion injury, asthma and inflammatory bowel diseases (IBD). Indeed, bilirubin shown to eliminate ROS production, so it is now considered as a promising therapeutic agent for ROS-mediated diseases, and can be used for the development of anti-oxidative nanomedicines. This review summarizes the current knowledge of the physiological mechanisms of ROS production and its role in pathological changes, and focuses to discuss the anti-oxidative effects of bilirubin, and its application in the experimental studies of nanomedicines. Previous studies have shown that bilirubin was mainly used as a responsive molecule in the microenvironment of ROS overproduction in neoplastic tissues for the development of anti-cancer nanodrugs, however it could also exert powerful ROS scavenging activity in chronic inflammation and ischemia/reperfusion injury. Therefore, bilirubin, as an inartificial ROS scavenger, is expected to be used for the development of nanomedicines against more diseases due to the universality of ROS involvement in human pathological conditions.