2. Academic Validation
  3. Biosafe cerium oxide nanozymes protect human pluripotent stem cells and cardiomyocytes from oxidative stress

Biosafe cerium oxide nanozymes protect human pluripotent stem cells and cardiomyocytes from oxidative stress

  • J Nanobiotechnology. 2024 Mar 26;22(1):132. doi: 10.1186/s12951-024-02383-x.
Chengwen Hang # 1 2 3 4,  Mohamed S Moawad # 5,  Zheyi Lin # 1 2 3 4 6,  Huixin Guo 7,  Hui Xiong 1 2 3 4 8,  Mingshuai Zhang 1 2 3 4 8,  Renhong Lu 1 2 3 4,  Junyang Liu 1 2 3 4 8,  Dan Shi 1 2 3 4,  Duanyang Xie 1 2 3 4 6,  Yi Liu 1 2 3 4 6,  Dandan Liang 1 2 3 4 6 9,  Yi-Han Chen 10 11 12 13 14 15,  Jian Yang 16 17 18 19 20 21
Affiliations

Affiliations

  • 1 State Key Laboratory of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • 2 Shanghai Arrhythmia Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • 3 Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • 4 Shanghai Frontiers Center of Nanocatalytic Medicine, Shanghai, 200092, China.
  • 5 Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza, 3725005, Egypt. msalah@cu.edu.eg.
  • 6 Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai, 200092, China.
  • 7 Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China.
  • 8 Department of Cell Biology, Tongji University School of Medicine, Shanghai, 200092, China.
  • 9 Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai, 200092, China.
  • 10 State Key Laboratory of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. yihanchen@tongji.edu.cn.
  • 11 Shanghai Arrhythmia Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. yihanchen@tongji.edu.cn.
  • 12 Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. yihanchen@tongji.edu.cn.
  • 13 Shanghai Frontiers Center of Nanocatalytic Medicine, Shanghai, 200092, China. yihanchen@tongji.edu.cn.
  • 14 Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai, 200092, China. yihanchen@tongji.edu.cn.
  • 15 Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai, 200092, China. yihanchen@tongji.edu.cn.
  • 16 State Key Laboratory of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. jy279@tongji.edu.cn.
  • 17 Shanghai Arrhythmia Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. jy279@tongji.edu.cn.
  • 18 Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. jy279@tongji.edu.cn.
  • 19 Shanghai Frontiers Center of Nanocatalytic Medicine, Shanghai, 200092, China. jy279@tongji.edu.cn.
  • 20 Department of Cell Biology, Tongji University School of Medicine, Shanghai, 200092, China. jy279@tongji.edu.cn.
  • 21 Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai, 200092, China. jy279@tongji.edu.cn.
  • # Contributed equally.
PMID: 38532378 DOI: 10.1186/s12951-024-02383-x
Abstract

Background: Cardiovascular diseases (CVDs) have the highest mortality worldwide. Human pluripotent stem cells (hPSCs) and their cardiomyocyte derivatives (hPSC-CMs) offer a valuable resource for disease modeling, pharmacological screening, and regenerative therapy. While most CVDs are linked to significant over-production of Reactive Oxygen Species (ROS), the effects of current Antioxidants targeting excessive ROS are limited. Nanotechnology is a powerful tool to develop Antioxidants with improved selectivity, solubility, and bioavailability to prevent or treat various diseases related to oxidative stress. Cerium oxide nanozymes (CeONZs) can effectively scavenge excessive ROS by mimicking the activity of endogenous antioxidant Enzymes. This study aimed to assess the nanotoxicity of CeONZs and their potential antioxidant benefits in stressed human embryonic stem cells (hESCs) and their derived cardiomyocytes (hESC-CMs).

Results: CeONZs demonstrated reliable nanosafety and biocompatibility in hESCs and hESC-CMs within a broad range of concentrations. CeONZs exhibited protective effects on the cell viability of hESCs and hESC-CMs by alleviating excessive ROS-induced oxidative stress. Moreover, CeONZs protected hESC-CMs from doxorubicin (DOX)-induced cardiotoxicity and partially ameliorated the insults from DOX in neonatal rat cardiomyocytes (NRCMs). Furthermore, during hESCs culture, CeONZs were found to reduce ROS, decrease Apoptosis, and enhance cell survival without affecting their self-renewal and differentiation potential.

Conclusions: CeONZs displayed good safety and biocompatibility, as well as enhanced the cell viability of hESCs and hESC-CMs by shielding them from oxidative damage. These promising results suggest that CeONZs may be crucial, as a safe nanoantioxidant, to potentially improve the therapeutic efficacy of CVDs and be incorporated into regenerative medicine.

Keywords

Cardiomyocytes; Cerium oxide nanozymes; Differentiation; Doxorubicin-induced cardiotoxicity; Human embryonic stem cells; Reactive oxygen species.

Figures
Products