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

• Published in: Journal of nanobiotechnology Vol. 22; no. 1; p. 132
• Main Authors: Hang, Chengwen, Moawad, Mohamed S, Lin, Zheyi, Guo, Huixin, Xiong, Hui, Zhang, Mingshuai, Lu, Renhong, Liu, Junyang, Shi, Dan, Xie, Duanyang, Liu, Yi, Liang, Dandan, Chen, Yi-Han, Yang, Jian
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 26-03-2024; BioMed Central; BMC
• Subjects: Analysis; Antioxidants; Apoptosis; Bioavailability; Biocompatibility; Cardiomyocytes; Cardiotoxicity; Cardiovascular diseases; Care and treatment; Cell culture; Cell growth; Cell self-renewal; Cell survival; Cell viability; Cerium; Cerium oxide nanozymes; Cerium oxides; Differentiation; Doxorubicin; Doxorubicin-induced cardiotoxicity; Embryo cells; Embryonic stem cells; Enzymes; Ethylenediaminetetraacetic acid; Fourier transforms; Health aspects; Heart cells; Homeostasis; Human embryonic stem cells; Hydrochloric acid; Hydrogen peroxide; Kinases; Medical screening; Metallic oxides; Nanomedicine; Nanoparticles; Nanotechnology; Neonates; Oxidative stress; Physiology; Pluripotency; Reactive oxygen species; Reagents; Regenerative medicine; Stem cells; Therapeutics, Experimental; China; Beijing China; United States > US; Japan; Human embryonic stem cells; Cardiomyocytes; Reactive oxygen species; Doxorubicin-induced cardiotoxicity; Differentiation; Cerium oxide nanozymes
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-024-02383-x

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).
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.
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.