ORIGINAL RESEARCH

Antioxidant activity and cellular response of novel cerium oxide nanoparticles stabilized with triethylene glycol under H2O2 stress in fibroblasts and keratinocytes

Viktoriia A. Anikina1* Daniil A. Kozlov2 Anton L. Popov3 Elizaveta A. Zamyatina1 Nelli R. Popova1*
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1 Isotope Research Laboratory, Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences, Pushchino, Moscow Oblast, Russia
2 Nanobiomaterials and Bioeffectors for the Theranostics of Socially Significant Diseases Laboratory, Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia
3 Theranostics and Nuclear Medicine Laboratory, Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences, Pushchino, Moscow Oblast, Russia
Submitted: 26 May 2025 | Revised: 19 September 2025 | Accepted: 9 October 2025 | Published: 10 November 2025
© 2025 by the Author(s). Licensee Biomaterials Translational, USA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 (CC BY-NC-SA 4.0) (https://creativecommons.org/licenses/by-nc-sa/4.0/deed.en)
Abstract

Oxidative stress has been demonstrated to play a key role in the process of skin injury and delayed wound healing. Consequently, the development of effective antioxidant nanomaterials has been identified as a promising strategy for dermatological applications. In this study, we synthesized ultra-small cerium oxide nanoparticles stabilized with triethylene glycol (CeNPs@TEG) using a single-step synthesis. We synthesized cerium oxide nanoparticles (CeNPs) with a size of 3 nm and a hydrodynamic diameter of 13 nm. The elevated triethylene glycol (TEG) content facilitated the formation of a stable sol without the necessity of additional surfactants, thereby preserving the surface activity of the CeNPs. The antioxidant activity of CeNPs@TEG was assessed using hydrogen peroxide (H2O2) as a representative reactive oxygen species (ROS), chosen for its stability and regulatory role in skin repair processes. At micromolar concentrations, CeNPs@TEG efficiently scavenged H2O2 in buffer solution, demonstrating strong ROS-neutralizing capacity. The cytotoxicity was evaluated in human fibroblasts and keratinocytes using MTT and Live/Dead assays. This confirmed the high level of biocompatibility and negligible effect on cell viability and activity of the reduced form of nicotinamide adenine dinucleotide phosphate (NADP-H)- dependent oxidoreductases. Pre-incubation of cells with CeNPs@TEG for 24 h prior to H2O2-induced oxidative stress exposure led to a significant reduction in intracellular ROS levels and enhanced activity of NADP-H-dependent oxidoreductases, indicating cytoprotective effects. The findings demonstrate that CeNPs@TEG combine an ultra-small size, high stability, low toxicity, and effective ROS scavenging, supporting their potential use in therapeutic strategies aimed at protecting skin cells from oxidative damage and enhancing wound healing.

Keywords
Biomedical application
Cerium oxide nanoparticles
Human fibroblast
Human keratinocytes
Oxidative stress
Triethylene glycol
Funding
This study was supported by the Russian Science Foundation (No. 22-63-00082).
Conflict of interest
The authors declare no conflicts of interest.
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