Ceria nanozyme coordination with curcumin for treatment of sepsis-induced cardiac injury by inhibiting ferroptosis and inflammation.

Schematic illustration of CeCH for sepsis-induced myocardial injury. (A) Preparation of CeCH with self-assembled by HSA. (B) The mechanism of CeCH to show protective effect for sepsis-induced cardiac injury by inhibiting ferroptosis and inflammation. [Display omitted] • CeCH was successfully developed by a green self-assembled method with human serum albumin to increase the water solubility and poor bioavailability of curcumin. • CeCH performed SOD-like and CAT-like activities to eliminate ROS generation and inhibit ferroptosis in H9C2 cells. • CeCH reduced the secretion of inflammatory factors by M1 macrophages to suppress the inflammation. • CeCH protected the heart against sepsis-induced cardiac injury and reversed cardiac dysfunction in vivo. • A promising strategy with Cur and nanozyme for septic cardiomyopathy by inhibiting ferroptosis and inflammation in clinical application. Sepsis-induced cardiac injury is the leading cause of death in patients. Recent studies have reported that reactive oxygen species (ROS)-mediated ferroptosis and macrophage-induced inflammation are the two main key roles in the process of cardiac injury. The combination of ferroptosis and inflammation inhibition is a feasible strategy in the treatment of sepsis-induced cardiac injury. In the present study, ceria nanozyme coordination with curcumin (CeCH) was designed by a self-assembled method with human serum albumin (HSA) to inhibit ferroptosis and inflammation of sepsis-induced cardiac injury. The formed CeCH obtained the superoxide dismutase (SOD)-like and catalase (CAT)-like activities from ceria nanozyme to scavenge ROS, which showed a protective effect on cardiomyocytes in vitro. Furthermore, it also showed ferroptosis inhibition to reverse cell death from RSL3-induced cardiomyocytes, denoted from curcumin. Due to the combination therapy of ceria nanozyme and curcumin, the formed CeCH NPs could also promote M2 macrophage polarization to reduce inflammation in vitro. In the lipopolysaccharide (LPS)-induced sepsis model, the CeCH NPs could effectively inhibit ferroptosis, reverse inflammation, and reduce the release of pro-inflammatory factors, which markedly alleviated the myocardial injury and recover the cardiac function. Overall, the simple self-assembled strategy with ceria nanozyme and curcumin showed a promising clinical application for sepsis-induced cardiac injury by inhibiting ferroptosis and inflammation. [ABSTRACT FROM AUTHOR]