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

Chengwen Hang ^1,2,3,4, Mohamed S Moawad ⁵, Zheyi Lin ^1,2,3,4,6

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

⁰State Key Laboratory of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.

Journal of Nanobiotechnology +

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March 27, 2024

View abstract on PubMed

Summary

Cerium oxide nanozymes (CeONZs) are safe and biocompatible nanoantioxidants. They protect human stem cells and cardiomyocytes from oxidative stress and doxorubicin-induced cardiotoxicity, offering potential for cardiovascular disease therapies.

Area Of Science

Biomedical Engineering
Nanotechnology
Stem Cell Biology

Background

Cardiovascular diseases (CVDs) are a leading cause of global mortality.
Human pluripotent stem cells (hPSCs) and cardiomyocytes (hPSC-CMs) are vital for disease modeling and regenerative medicine.
Existing antioxidants have limited efficacy against excessive reactive oxygen species (ROS) in CVDs.

Purpose Of The Study

To evaluate the nanotoxicity and antioxidant potential of cerium oxide nanozymes (CeONZs).
To assess CeONZs' effects on human embryonic stem cells (hESCs) and derived cardiomyocytes (hESC-CMs) under oxidative stress.

Main Methods

Assessed nanosafety and biocompatibility of CeONZs in hESCs and hESC-CMs.
Investigated CeONZs' protective effects against ROS-induced oxidative stress.
Examined CeONZs' efficacy in mitigating doxorubicin (DOX)-induced cardiotoxicity in hESC-CMs and neonatal rat cardiomyocytes (NRCMs).

Main Results

CeONZs demonstrated nanosafety and biocompatibility across a wide concentration range in hESCs and hESC-CMs.
CeONZs alleviated oxidative stress, enhancing cell viability in hESCs and hESC-CMs.
CeONZs protected hESC-CMs from DOX-induced cardiotoxicity and reduced ROS, apoptosis, and enhanced survival in hESCs without impacting their stemness.

Conclusions

CeONZs exhibit excellent safety and biocompatibility, acting as effective nanoantioxidants.
CeONZs enhance hESC and hESC-CM viability by protecting against oxidative damage.
CeONZs show promise as a therapeutic agent for cardiovascular diseases and in regenerative medicine.

Keywords:

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

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