Calcein-Modified CeO2 for Intracellular ROS Detection: Mechanisms of Action and Cytotoxicity Analysis In Vitro

Nikita N Chukavin; Vladimir K Ivanov; Anton L Popov

doi:10.3390/cells12192416

Calcein-Modified CeO₂ for Intracellular ROS Detection: Mechanisms of Action and Cytotoxicity Analysis In Vitro

Cells. 2023 Oct 7;12(19):2416. doi: 10.3390/cells12192416.

Authors

Nikita N Chukavin^{1

2}, Vladimir K Ivanov³, Anton L Popov¹

Affiliations

¹ Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Moscow 142290, Russia.
² Scientific and Educational Center, State University of Education, Moscow 105005, Russia.
³ Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences, Moscow 119991, Russia.

Abstract

Cerium oxide nanoparticles (CeO₂ NPs) are metal-oxide-based nanozymes with unique reactive oxygen species (ROS) scavenging abilities. Here, we studied new CeO₂ NPs modified with calcein (CeO₂-calcein) as an intracellular ROS inactivation/visualization theranostic agent. The molecular mechanisms of the CeO₂-calcein intracellular activity, allowing for the direct monitoring of ROS inactivation in living cells, were studied. CeO₂-calcein was taken up by both normal (human mesenchymal stem cells, hMSc) and cancer (human osteosarcoma, MNNG/Hos cell line) cells, and was easily decomposed via endogenous or exogenous ROS, releasing brightly fluorescent calcein, which could be quantitatively detected using fluorescence microscopy. It was shown that the CeO₂-calcein has selective cytotoxicity, inducing the death of human osteosarcoma cells and modulating the expression of key genes responsible for cell redox status as well as proliferative and migration activity. Such cerium-based theranostic agents can be used in various biomedical applications.

Keywords: antioxidant; calcein; cerium oxide nanoparticles; reactive oxygen species.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bone Neoplasms*
Cerium* / pharmacology
Humans
Metal Nanoparticles*
Osteosarcoma* / drug therapy
Reactive Oxygen Species / metabolism

Substances

Reactive Oxygen Species
fluorexon
Cerium

Grants and funding

This research was funded by the Ministry of Science and Higher Education of the Russian Federation for the Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences (State Assignment: 075-01025-23-01).