Curcumin-encapsulated ROS-responsive nanoparticles for modulation of oxidative stress and inflammation in sepsis.

Sepsis is a life-threatening syndrome characterized by excessive oxidative stress and uncontrolled inflammation, ultimately leading to multiple organ dysfunction. Curcumin has shown considerable potential for the treatment of sepsis due to its antioxidant and anti-inflammatory properties; however, its clinical application is limited by poor water solubility, low bioavailability, and instability. Herein, a reactive oxygen species (ROS)-responsive nanoplatform (Cur@NPs) was developed for curcumin delivery by encapsulating curcumin into self-assembled mPEG-b-PPS nanoparticles. The resulting Cur@NPs exhibited an appropriate particle size, high encapsulation efficiency, and good colloidal stability. In addition, Cur@NPs showed oxidation-triggered drug release and effectively scavenged multiple ROS species under oxidative conditions. In vitro studies demonstrated that Cur@NPs markedly reduced intracellular ROS levels and suppressed the production of pro-inflammatory mediators, including TNF-α, IL-6, and NO, in LPS-stimulated macrophages. In an LPS-induced murine sepsis model established via intraperitoneal injection, Cur@NPs significantly attenuated systemic inflammation and alleviated multiple organ injury. Collectively, these findings suggest that Cur@NPs provide an effective ROS-responsive curcumin delivery strategy and may serve as a candidate nanoplatform for further sepsis studies.