International Journal of Nanomedicine (Aug 2021)
Size-Dependent Cytotoxicity and Reactive Oxygen Species of Cerium Oxide Nanoparticles in Human Retinal Pigment Epithelia Cells
Abstract
Yuanyuan Ma,1,* Peng Li,2,* Laien Zhao,1 Jia Liu,1 Jinguo Yu,3 Yanmei Huang,1 Yuting Zhu,1 Zelin Li,1 Ruikang Zhao,1 Shaofeng Hua,1 Yanping Zhu,1 Zhuhong Zhang1 1School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People’s Republic of China; 2Department of Nephrology Yantai Yuhuangding Hospital, Qingdao University, Yantai, 264005, Shandong, People’s Republic of China; 3Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhuhong ZhangSchool of Pharmacy, Yantai University, 30 Qingquan Road, Yantai, Shandong Province, 264005, People’s Republic of ChinaTel +86 18526851691Email [email protected]: The use of cerium oxide nanoparticles (CeO2 NPs), a lanthanide element oxide and bivalent compound, has been growing continuously in industry and biomedicine. Due to their wide application, the potential human health problems of CeO2 NPs have attracted attention, but studies on the toxicity of this compound to human eyes are lacking. This study investigated the cytotoxicity and reactive oxygen species (ROS) of CeO2 NPs in human retinal pigment epithelial cells (ARPE-19 cells).Methods: Using the transmission electron microscope (TEM), the size distribution and shape of CeO2 NPs were characterized. To explore the effect of CeO2 NP size on ophthalmic toxicity in vitro, three sizes (15, 30 and 45 nm) of CeO2 NPs were investigated using ATP content measurement, LDH release measurement and cell proliferation assay in ARPE-19 cells. ROS values and mitochondrial membrane potential depolarization were evaluated by H2DCF-DA staining and JC-1 staining. Morphology changes were detected using a phase-contrast microscope.Results: The cytotoxicity of 15 nm CeO2 NPs was found to be the highest and hence was further explored. Treatment with 15 nm CeO2 NPs caused the morphology of ARPE-19 cells to change in a dose- and time-dependent manner. Moreover, the treatment induced excessive ROS generation and mitochondrial membrane potential depolarization. In addition, cytotoxicity was attenuated by the application of a ROS scavenger N-acetyl-L- cysteine (NAC).Conclusion: CeO2 NPs induced cytotoxicity in ARPE-19 cells and excessive production of ROS and decreasing mitochondrial membrane potential. The Overproduction of ROS partially contributes to CeO2 NP-induced cytotoxicity.Keywords: nanomaterials, ophthalmic toxicity, oxidative stress, mitochondrial membrane potential depolarization
