Ceria Nanozyme Coordination with Curcumin for Treatment of Sepsis-induced Cardiac Injury by Inhibiting Ferroptosis and Inflammation

Chenxiao Jiang; Qianzhi Shi; Jing Yang; Hao Ren; Lu Zhang; Shan Chen; Jiayi Si; Yihai Liu; Dujuan Sha; Biao Xu; Jie Ni

doi:10.1016/j.jare.2023.10.011

Ceria Nanozyme Coordination with Curcumin for Treatment of Sepsis-induced Cardiac Injury by Inhibiting Ferroptosis and Inflammation

J Adv Res. 2023 Oct 21:S2090-1232(23)00315-6. doi: 10.1016/j.jare.2023.10.011. Online ahead of print.

Authors

Chenxiao Jiang¹, Qianzhi Shi², Jing Yang³, Hao Ren³, Lu Zhang², Shan Chen⁴, Jiayi Si², Yihai Liu⁵, Dujuan Sha⁶, Biao Xu⁵, Jie Ni⁷

Affiliations

¹ Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China.
² Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210008, China.
³ School of Pharmaceutical Science, Nanjing Tech University, Nanjing, Jiangsu 211816, China.
⁴ Department of General Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China.
⁵ Department of Cardiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China.
⁶ Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210008, China; Department of General Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China.
⁷ Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210008, China; Department of Emergency Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China. Electronic address: nijie@njglyy.com.

PMID: 37871772
DOI: 10.1016/j.jare.2023.10.011

Abstract

Introduction: 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.

Objectives: 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.

Methods and results: 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.

Conclusion: 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.

Acknowledgments: This study was supported by grants of the National Natural Science Foundation of China (82100398); the Nanjing Medical Science and Technique Development Foundation (YKK21068); Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (2023-LCYJ-PY-24); the Jiangsu Research Hospital Association for Precision Medication (JY202120); the Jiangsu Pharmaceutical Association for Jinpeiying Project (J2021001); China Postdoctoral Science Foundation (2022M721576).

Keywords: Ceria nanozyme; Curcumin; Ferroptosis; Inflammation; Sepsis-induced cardiac injury.