Hydrogen peroxide-activatable polymeric prodrug of curcumin for ultrasound imaging and therapy of acute liver failure

Abstract Curcumin is a major active phenolic component of turmeric and has gained great attention in pharmaceutics due to its potent antioxidant, anti-inflammatory and anticancer activity. Here, we developed poly(oxalate- co -curcumin) (POC) as a hydrogen peroxide (H 2 O 2 )-activatable polymeric prodrug of curcumin by incorporating curcumin in the backbone of H 2 O 2 -responsive polyoxalate. POC particles effectively scavenged H 2 O 2 and released curcumin in a H 2 O 2 -triggered manner. POC particles exhibited excellent antioxidant and anti-inflammatory activity in activated cells. POC particles intravenously administrated into acetaminophen-intoxicated mice remarkably suppressed the level of alanine transaminase and inhibited apoptotic cell death in liver. Interestingly, POC particles could also enhance the ultrasound contrast in the intoxicated liver due to CO 2 bubble generation through H 2 O 2 -triggered oxidation of peroxalate esters. Given their H 2 O 2 -responsiveness and highly potent antioxidant activity, POC particles hold great translational potential as theranostic agents for H 2 O 2 -associated diseases.