Advantages and Potential Benefits of Using Organoids in Nanotoxicology.

Organoids are microtissues that recapitulate the complex structural organization and functions of tissues and organs. Nanoparticles have several specific properties that must be considered when replacing animal models with in vitro studies, such as the formation of a protein corona, accumulation, ability to overcome tissue barriers, and different severities of toxic effects in different cell types. An increase in the number of articles on toxicology research using organoid models is related to an increase in publications on organoids in general but is not related to toxicology-based publications. We demonstrate how the quantitative assessment of toxic changes in the structure of organoids and the state of their cell collections provide more valuable results for toxicological research and provide examples of research methods. The impact of the tested materials on organoids and their differences are also discussed. In conclusion, we highlight the main challenges, the solution of which will allow researchers to approach the replacement of in vivo research with in vitro research: biobanking and standardization of the structural characterization of organoids, and the development of effective screening imaging techniques for 3D organoid cell organization.

Magnetic Patterning of Tissue Spheroids Using Polymer Microcapsules Containing Iron Oxide Nanoparticles.

Magnetic tissue engineering is one of the rapidly emerging and promising directions of tissue engineering and biofabrication where the magnetic field is employed as temporal removal support or scaffold. Iron oxide nanoparticles are used to label living cells and provide the desired magnetic properties. Recently, polymer microcapsules loaded with iron oxide nanoparticles have been proposed as a novel approach to designing magnetic materials with high local concentrations. These microcapsules can be readily internalized and retained intracellularly for a long time in various types of cells. The low cytotoxicity of these microcapsules was previously shown in 2D cell culture. This paper has demonstrated that cells containing these nontoxic nanomaterials can form viable 3D tissue spheroids for the first time. The spheroids retained labeled fluorescent microcapsules with magnetic nanoparticles without a detectable cytotoxic effect. The high concentration of packed nanoparticles inside the microcapsules enables the evident magnetic properties of the labeled spheroids to be maintained. Finally, magnetic spheroids can be effectively used for magnetic patterning and biofabrication of tissue-engineering constructs.

Nanosafety vs. nanotoxicology: adequate animal models for testing in vivo toxicity of nanoparticles.

Nanotoxicological studies using existing models of normal cells and animals often encounter a paradox: retention of nanoparticles in intracellular compartments for a long time is not accompanied by any significant toxicological effects. Can we expect that the revealed changes will be not harmful after translation to practice, outside of a sterile laboratory and ideally healthy organisms? Age-associated and pathological processes can affect target organs, metabolism, and detoxification in the mononuclear phagocyte system organs and change biodistribution routes, thus making the use of nanomaterial not safe. The potential solution to this issue can be testing the toxic properties of nanoparticles in animal models with chronic diseases. However, current studies of nanotoxicity in animal models with a brain, cardiovascular system, liver, digestive tract, reproductive system, and skin diseases are unsystematic. Even though these studies demonstrate the emergence of new toxic effects that are not present in healthy animals. In this regard, we set the goal of this review as the formulation of the requirements for an animal model capable of assessing the potential toxicity of nanoparticles based on the nanosafety approach.

Organ-specific toxicity of magnetic iron oxide-based nanoparticles.

The unique properties of magnetic iron oxide nanoparticles determined their widespread use in medical applications, the food industry, textile industry, which in turn led to environmental pollution. These factors determine the long-term nature of the effect of iron oxide nanoparticles on the body. However, studies in the field of chronic nanotoxicology of magnetic iron particles are insufficient and scattered. Studies show that toxicity may be increased depending on oral and inhalation routes of administration rather than injection. The sensory nerve pathway can produce a number of specific effects not seen with other routes of administration. Organ systems showing potential toxic effects when injected with iron oxide nanoparticles include the nervous system, heart and lungs, the thyroid gland, and organs of the mononuclear phagocytic system (MPS). A special place is occupied by the reproductive system and the effect of nanoparticles on the health of the first and second generations of individuals exposed to the toxic effects of iron oxide nanoparticles. This knowledge should be taken into account for subsequent studies of the toxicity of iron oxide nanoparticles. Particular attention should be paid to tests conducted on animals with pathologies representing human chronic socially significant diseases. This part of preclinical studies is almost in its infancy but of great importance for further medical translation on nanomaterials to practice.

Memristive TiO2: Synthesis, Technologies, and Applications.

Titanium dioxide (TiO2) is one of the most widely used materials in resistive switching applications, including random-access memory, neuromorphic computing, biohybrid interfaces, and sensors. Most of these applications are still at an early stage of development and have technological challenges and a lack of fundamental comprehension. Furthermore, the functional memristive properties of TiO2 thin films are heavily dependent on their processing methods, including the synthesis, fabrication, and post-fabrication treatment. Here, we outline and summarize the key milestone achievements, recent advances, and challenges related to the synthesis, technology, and applications of memristive TiO2. Following a brief introduction, we provide an overview of the major areas of application of TiO2-based memristive devices and discuss their synthesis, fabrication, and post-fabrication processing, as well as their functional properties.

The Effect of Short-Term Physical Activity on the Oxidative Stress in Rats with Different Stress Resistance Profiles in Cerebral Hypoperfusion.

Oxidative stress associated with chronic cerebral hypoperfusion is one of the fundamental factors leading to neurodegenerative diseases. To prevent oxidative stress, physical activity is effective. Physical exercise enables development of rehabilitation techniques that can progressively increase patients' stress resistance. We determined the oxidative stress dynamics in experimental hypoperfusion and modeled rehabilitation measures, comparing sex and stress resistance levels. The experiment was performed on 240 Wistar rats of both sexes over a period of 90 days. Based on behavioral test results obtained using the open field test, the rats were divided into active animals with predicted higher stress resistance (HSR) and passive animals with predicted lower stress resistance (LSR). TBA (thiobarbituric acid) plasma concentration of the active products (malondialdehyde-MDA), blood plasma (NO-X) concentration, and L-citrulline (LC) concentration were determined spectrophotometrically at the corresponding wave length (nm). The intensity of oxidative stress was evaluated using the chemoluminscent method to determine the blood plasma antioxidant activity on the BCL-07 biochemoluminometer. This study revealed two stages of oxidative stress: a less pronounced phase covering the first days after surgery and a main one, which starts from the month after the operation to 3 months. Female sex and a high initial level of stress resistance reduced the severity of oxidative stress. Physical activity commencing a week after the surgery resulted in "reloading" the adaptive mechanisms and slowed the onset of the main stage, leading to a decrease in the free-radical process in all studied subgroups and the greater blood plasma (NO)-X decrease in the male animals. Future neuropharmacological intervention most likely will be able to determine the pathophysiology mechanism of chronic brain hypoperfusion and potentially extending adaptive responses.

Toxicity Patterns of Clinically Relevant Metal Oxide Nanoparticles.

Nanostructured drugs are being approved for clinical use, although there is a serious deficit of systematic studies of these materials. Data on toxicity of nanoparticles (NPs) can vary due to different methods of preparation, size, and shape. We investigated the toxicity against cultured human cells, the acute toxicity in mice, and the influence on conjugative transfer of antibiotic resistance genes of clinically relevant NPs such as TiO2, ZrO2, HfO2, Ta2O5, Fe3O4, and AlOOH. NPs were synthesized as aqueous sols by the same method in aqueous solution, with almost identical size 2-10 nm. None of these NPs was cytotoxic at concentrations compatible with water solubility. Furthermore, TiO2, HfO2, Ta2O5, Fe3O4, and AlOOH were not toxic to mice after oral administration. However, ZrO2 showed rather high toxicity, with LD50 2277.8 mg/kg. Experiments with plasmid transfer between bacteria demonstrated that AlOOH NPs were the most hazardous since this material promoted the emergence of resistance to antibiotics. Thus, although our metal oxide NPs are largely non-toxic, their properties may differ in specific biological situations.