In the ongoing search for practical uses of rare-earth metal nanoparticles, cerium dioxide nanoparticles (nanoceria) have received special attention. The purpose of this research was to study the biomedical effects of nanocrystalline forms of cerium oxide obtained by different synthesis schemes and to evaluate the effect of different concentrations of nanoceria (from 10⁻² to 10⁻⁶ M) on cells involved in the regeneration of skin cell structures such as fibroblasts, mesenchymal stem cells, and keratinocytes. Two different methods of nanoceria preparation were investigated: (1) CeO-NPs-1 by precipitation from aqueous solutions of cerium (III) nitrate hexahydrate and citric acid and (2) CeO-NPs-2 by hydrolysis of ammonium hexanitratocerate (IV) under conditions of thermal autoclaving. According to the X-ray diffraction, transmission electron microscopy, and dynamic light scattering data, CeO₂-1 consists of individual particles of cerium dioxide (3–5 nm) and their aggregates with diameters of 60–130 nm. CeO₂-2 comprises small aggregates of 8–20 nm in diameter, which consist of particles of 2–3 nm in size. Cell cultures of human fibroblasts, human mesenchymal stem cells, and human keratinocytes were cocultured with different concentrations of nanoceria sols (10⁻², 10⁻³, 10⁻⁴, 10⁻⁵, and 10⁻⁶ mol/L). The metabolic activity of all cell types was investigated by MTT test after 48 and 72 h, whereas proliferative activity and cytotoxicity were determined by quantitative cell culture counting and live/dead test. A dependence of biological effects on the method of nanoceria preparation and concentration was revealed. Data were obtained with respect to the optimal concentration of sol to achieve the highest metabolic effect in the used cell cultures. Hypotheses about the mechanisms of the obtained effects and the structure of a fundamentally new medical device for accelerated healing of skin wounds were formulated. The method of nanoceria synthesis and concentration fundamentally and significantly change the biological activity of cell cultures of different types—from suppression to pronounced stimulation. The best biological activity of cell cultures was determined through cocultivation with sols of citrate nanoceria (CeO-NPs-1) at a concentration of 10⁻³–10⁻⁴ M.

Layer-by-layer (LbL) self-assembled polyelectrolyte capsules have demonstrated their unique advantages and capability in drug delivery applications. These ordered micro/nanostructures are also promising candidates as imaging contrast agents for diagnostic and theranostic applications. Magnetic resonance imaging (MRI), one of the most powerful clinical imaging modalities, is moving forward to the molecular imaging field and requires advanced imaging probes. This paper reports on a new design of MRI-visible LbL capsules, loaded with redox-active gadolinium-doped cerium oxide nanoparticles (CeGdO_2−x NPs). CeGdO_2−x NPs possess an ultrasmall size, high colloidal stability, and pronounced antioxidant properties. A comprehensive analysis of LbL capsules by TEM, SEM, LCSM, and EDX techniques was carried out. The research demonstrated a high level of biocompatibility and cellular uptake efficiency of CeGdO_2−x-loaded capsules by cancer (human osteosarcoma and adenocarcinoma) cells and normal (human mesenchymal stem) cells. The LbL-based delivery platform can also be used for other imaging modalities and theranostic applications.

The use of various nanoformulations for cancer radiotherapy has great potential due to their increased effectiveness and safety. At the stage of preclinical evaluation of such nanoformulations in vitro, they are tested on monolayers of tumor cell cultures, which is an unrealistic representation of tumors in vivo, which leads to an inaccurate selection of suitable drugs. To solve this problem, 3D cellular spheroids are becoming an additional tool for confirming the effectiveness of new therapeutic nanoformulations. Here we show the possibility of using citrate-stabilized cerium oxide nanoparticles (nanoceria, CeO2 NPs) as a nanoradiosensitizer in an experimental 3D model of tumor spheroids formed from 4T1 human breast cancer cells. It has been shown that ultra-small size (about 1-2 nm) CeO2 NPs have pH-sensitive radiocatalytic activity, increasing the generation of ROS under irradiation conditions. It has been shown that preloading of CeO2 NPs into a cellular spheroid at a micromolar concentrations does not adversely affect the rate of spheroid formation and its final size. However, such preloading has a pronounced inhibitory effect on the rate of cell migration from the spheroid after X-ray irradiation and also reduces their clonogenic activity. Thus, CeO2 NPs can be considered as a promising nanoradiosensitizer for radiotherapy of tumors.