induce mitochondrial dysfunction through oxidative stress, followed by induction of cytoskeleton disorganization and morphological changes in the cell membrane (Pi et al. 2013).
An important factor of ruthenium‐modified SeNPs is the ability to influence angiogenesis and cause its inhibition. The regulation of angiogenesis is known to be a promising area for the treatment of tumors since the uncontrolled growth of cancer cells directly depends on adequate blood supply. Ruthenium‐modified SeNPs (Ru‐SeNPs) can interact with proteins located in the cytoplasm. These NPs are localized mainly in the cytoplasm and perinuclear space. Then they penetrate the nucleus membrane and cause DNA fragmentation, as well as damage to the plasma membrane. Ruthenium‐modified SeNPs have the ability to inhibit proliferation, endothelial cell migration, and further blood vessel formation by blocking the main fibroblast growth factor (FGFb) and its receptor (FGFR1) (Sun et al. 2013). However, Ru‐SeNPs are 2–6 times more toxic than SeNPs (Chaudhary et al. 2014). Se‐substituted hydroxyapatite NPs have low toxicity and reduce the expression of Ki‐67 (a marker of proliferative activity of tumor cells), vascular endothelial growth factor (VEGF), and matrix metallopeptidase 9 (MMP‐9) (Yanhua et al. 2016). Important for the antitumor effect is the ability of SeNPs to stop the cell cycle. Thus, Se‐substituted hydroxyapatite NPs in hepatocellular carcinoma cells, in addition to damage of the cancer cell DNA, inhibit the expression of Cdk1 protein and stop the cell cycle in the S‐G2/M phase (Yanhua et al. 2016).
SeNPs in MDA‐MB‐231 breast tumor cells delay phase S of the cell cycle, during which nuclear DNA replication occurs (Khurana et al. 2019). Due to the delay in phase S, the cell cannot go to the next phase G2, the apoptosis program is started and proliferation is inhibited (Luo et al. 2012). SeNPs have an antitumor effect by affecting the activity of individual genes. SeNPs increase expression of aldo‐keto reductase family 1 member B10 and inhibitor of growth protein 3 and decrease expression of forkhead box protein P1 (Ahmed et al. 2014). To date, numerous studies with SeNPs are ongoing on cell cultures, organs, and biological organisms in general. A lot of involved molecules, systems, and pathways were revealed. However, many of the effects of SeNPs remain unclear and require further research.
3.5 Conclusion
Thus, nanoscale elemental Se is not only biocompatible, but also has a number of biological activities (antitumor, antimicrobial, protective). The biological properties of SeNPs, such as toxicity, selectivity for various cell types, biocompatibility, and biodegradability, as well as the presence of specific activities, are directly dependent on their physical and chemical properties. Particular attention in the synthesis is given to the ability to control the size, shape, composition, and uniformity of the resulting NPs. To date, data on the toxicity and safety of SeNPs are accumulating. Se in nanoscale form has a dose‐dependent effect. High concentrations of SeNPs (above 2 mg Se per kg of animal weight) can cause Se‐induced toxicity in mammals.
Many publications devoted the possibility of using Se nanoforms in medicine. Therefore, further studies related to the safety and mechanisms of action of SeNPs are promising.
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