Utilizing stimuli-responsive nanoparticles to deliver and enhance the anti-tumor effects of bilirubin

Bilirubin (BR) is among the most potent endogenous antioxidants that originates from the heme catabolic pathway. Despite being considered as a dangerous and cytotoxic waste product at high concentrations, BR has potent antioxidant effects leading to the reduction of oxidative stress and inflammation, which play an important role in the development and progression of cancer. The purpose of this study is to introduce PEGylated BR nanoparticles (NPs), themselves or in combination with other anti-cancer agents. BR is effective when loaded into various nanoparticles and used in cancer therapy. Interestingly, BRNPs can be manipulated to create stimuliresponsive carriers providing a sustained and controlled, as well as on-demand, release of drug in response to internal or external factors such as reactive oxygen species, glutathione, light, enzymes, and acidic pH. This review suggests that BRNPs have the potential as tumor microenvironment-responsive delivery systems for effective targeting of various types of cancers.