Synthesis and biocompatibility study of ceria-mildronate nanocomposite in vitro

Nanoscale cerium dioxide (CeO$_2$, nanoceria) possesses notable redox activity, which is actively used in advanced biomedical applications. The low toxicity, high biocompatibility and antioxidant activity of nanoceria make it a new generation nanozyme with a unique activity. Combination of nanoceria with various biologically active substances results in organic-inorganic nanocomposites possessing enhanced activity. Here, we synthesized a novel organic-inorganic hybrid material (Mil-CeO$_2$) based on 2-(2-carboxylatoethyl)-1,1,1-trimethylhydrazinium and nanoceria, which has an ultra-small particle size, high antioxidant activity and pronounced biological activity. The analysis of cytotoxicity of the composite did not reveal any negative effects on the NCTC L929 mouse fibroblasts at concentrations below 10 mM. It was shown that the nanocomposite did not cause morphological changes in cells, or lead to cell death and mitochondrial membrane potential disruption, while maintaining viability in mouse fibroblasts in vitro. Additionally, we showed that Mil-CeO$_2$ is capable of protecting cells from hydrogen peroxide (H$_2$O$_2$)-induced or radiation-induced oxidative stress.