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Turovsky, E.A.; Baryshev, A.S.; Plotnikov, E.Y. Nanoparticles for Brain Protection. Encyclopedia. Available online: https://encyclopedia.pub/entry/54405 (accessed on 19 May 2024).
Turovsky EA, Baryshev AS, Plotnikov EY. Nanoparticles for Brain Protection. Encyclopedia. Available at: https://encyclopedia.pub/entry/54405. Accessed May 19, 2024.
Turovsky, Egor A., Alexey S. Baryshev, Egor Y. Plotnikov. "Nanoparticles for Brain Protection" Encyclopedia, https://encyclopedia.pub/entry/54405 (accessed May 19, 2024).
Turovsky, E.A., Baryshev, A.S., & Plotnikov, E.Y. (2024, January 26). Nanoparticles for Brain Protection. In Encyclopedia. https://encyclopedia.pub/entry/54405
Turovsky, Egor A., et al. "Nanoparticles for Brain Protection." Encyclopedia. Web. 26 January, 2024.
Nanoparticles for Brain Protection
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This entry is adapted from the peer-reviewed paper 10.3390/nano14020160

Strokes rank as the second most common cause of mortality and disability in the human population across the world. Currently, available methods of treating or preventing strokes have significant limitations, primarily the need to use high doses of drugs due to the presence of the blood–brain barrier. In the last decade, increasing attention has been paid to the capabilities of nanotechnology. However, the vast majority of research in this area is focused on the mechanisms of anticancer and antiviral effects of nanoparticles.

nanomaterials selenium selenium nanoparticles

1. Nanoparticles as Regulators of Cellular Redox Status

The range of nanoparticles produced and studied in the context of the problem of strokes is quite wide. Nanoparticles made of metals and metal oxides, which primarily include nanoparticles of cerium oxide (CeNPs), aurum (AuNPs), and platinum (PtNPs), are known. Both of these types of nanoparticles are ROS-scavenging and have catalytic activity, imitating the properties of superoxide dismutase (SOD) and catalase (CAT) and converting •OH into O2 [1][2][3]. It has been shown that AuNPs and CeNPs can act as both antioxidants and pro-oxidants. Additionally, the toxic effect of AuNPs is determined by their diameter, when 20 nm AuNPs can reduce cerebral infarction in rats, while 5 nm AuNPs lead to enlarged infarction [4]. CeNPs have a neuroprotective effect and suppress OGD or H2O2-induced ROS production in a narrow concentration range of approximately 10 μg/mL, while higher concentrations of nanoceria induce ROS production by astrocytes [5].
Carbon-based nanoparticles, which are highly stable and are most often presented in the form of fullerenes and carbon nanotubes, have been used. Fullerenes (C60 nanoparticles) are spherical in shape, have abundant conjugated double bonds, and have the ability to absorb electrons. Therefore, they can perform the same function as SOD and scavenging free radicals [6]. The electrospun nanofiber scaffold, modified with 10 nm AuNPs, promoted immature neurons to grow axons more than branched trees [7]. Carbon-based nanoparticles are also easy to modify and easily adsorb active compounds on the surface. Carbon-based nanoparticles also exert a neuroprotective effect against oxidative stress and reduce the volume of cerebral infarction by 50% [8]. Fullerene nanoparticles activate the c-Jun NH2 terminal protein kinase (JNK) in the brain microvascular endothelial cells and inhibit the cleavage of polyADP-ribose polymerase (PARP) to inhibit cell apoptosis [9]. At the same time, carbon nanotubes are characterized by a significant limitation: they are not biodegradable in the body and easily form large aggregates.
Liposome nanoparticles are composed of amphiphilic molecules similar to biological membranes, which have also been used. Due to their properties, this type of nanoparticle is characterized by good biocompatibility and biodegradability, which allows them to be used as a shuttle for transporting active substances to the brain [10]. Polymeric nanoparticles are the most commonly used nanomaterials in drug delivery and are praised for their excellent biocompatibility and biodegradability. Polymeric nanoparticles are made of natural polymers (e.g., chitosan) or synthetic polymers (e.g., poly(lactic-co-glycolic acid) (PLGA), polylactide (PLA), poly(amidoa-mine) (PAMAM), or poly(methyl methacrylate) (PMMA)), and these materials have great surface modulation potential and good pharmacokinetic characteristics [11]. However, liposome nanoparticles and polymeric nanoparticles have limitations: an expensive production protocol, a relatively short “lifetime”, and the complexity of the process of their stabilization. It has been shown that polystyrene nanomaterials are changed from a sphere to a disk, with lower cell uptake and little impact on cell functions, such as cellular ROS generation [12].
Of particular interest are nanoparticles obtained from selenium (Se), which belongs to a class of lanthanides and is a non-metal. Most Se compounds, organic and inorganic, are easily absorbed from food and transported to the liver, the main organ of Se metabolism. A large number of methods can be used to synthesize selenium nanostructures, such as sonochemical synthesis, hydrothermal method, electrodeposition, physical adsorption via gas phase diffusion, laser ablation of a massive target, etc. [13][14][15]. Nanostructures of various shapes: trigonal, nanorods, nanoribbons, hexagonal prism, nanoplates, nanotubes, and spheres are obtained from selenium [16]. SeNPs, like nanoparticles of other origins, can enhance the effectiveness of ionized drug materials, improve the transport of water-soluble drugs, peptides, and many proteins, siRNAs, miRNAs, DNAs, i.e., used as nanotransporters of drugs to the brain. For selenium nanoparticles, it was shown that their modification with monoclonal antibodies (OX26) led to the activation of antioxidant systems of brain cells during ischemia, suppression of inflammation, and apoptosis [17]. At the same time, there are studies that demonstrate that SeNPs, without modification, are capable of activating protective signaling pathways, so the need for such active particles with additional molecules remains questionable. It was found that selenium activates transcriptional factors TFAP2C and SP1 to enhance GPx4 expression. In the bleeding brain stroke model, a single dose of selenium enters the brain, and it can promote the expression of the antioxidant GPx4 protein and protect the neurons [18].

2. The Effect of the Shape and Diameter of Nanoparticles on Their Cytoprotective Properties

The most important characteristics of nanoparticles that determine their effectiveness are their diameter and size. It is known that the use of nanoparticles for emergent large vessel occlusion has significant limitations. It has been shown that very small-sized nanoparticles (<10 nm) can rapidly clear through glomerular filtration and will be excreted, whereas too large-sized nanoparticles could impede their transport into the clot, carrying thrombolytic agents, or their transport of neuroprotective agents to the penumbra [19][20]. There are also results obtained from studies of the cytotoxic effects of nanoparticles, which demonstrate that small nanomaterials have greater activity but act within a few hours. For example, aurum nanoparticles are non-toxic with a diameter of 15 nm and are used as an effective nanotransporter for active compounds, but with a diameter of less than 5 nm (0.8–1.8 nm), they have an extremely cytotoxic effect [21]. The effects of nanoparticle shape and size have been explored to some extent in cancer cells. Thus, on cell lines A549, HepG2, MCF-7, and CGC-7901, it was shown that 5 nm-sized AgNPs are more toxic compared to 20 nm and 50 nm, causing a significantly more pronounced release of lactate dehydrogenase [22][23]. At the same time, there are practically no studies on “healthy” cells, including brain cells. It was found that silver nanoparticles (AgNPs) with a size of less than 50 nm showed a decrease in the percentage of living human mesenchymal stem cells after incubation for 1 h with a concentration of 10 μg/mL, while the use of 100 μg/mL nanoparticles with sizes of 10 and 20 nm does not affect the survival of progenitor human adipose-derived stem cells, which normally differentiate even after 24 h incubation [24][25]. There is convincing evidence that selenium nanoparticles with a diameter of a micrometer or more are biologically inert [26], while subnanomolar nanoparticles, on the contrary, are extremely toxic to cancer cells [27]. Indeed, SeNPs with a diameter of 36 nm are more bioavailable to eukaryotic cells than selenite or selenomethionine. When exposed to SeNPs of this diameter, the activity of glutathione peroxidases and thioredoxin reductases increases, providing an antioxidant effect [27].
As for the shape of nanoparticles, there is even less research in this area compared to the mechanisms of the influence of the diameter of nanoparticles on the functions of nerve cells. Research in this area is focused on determining the circulation time of large filament-shaped nanoparticles in the bloodstream. It is precisely this physical feature that suggests the prospects of their use in therapy. It has been established that the residence time of long rod nanoparticles and short rod silica nanoparticles in the gastrointestinal system is significantly higher compared to spherical nanoparticles [28][29]. It is believed that the nanofilament may promote neuronal attachment and enhance the rate of neurite outgrowth [30][31]. It has been established that carbon nanotubes are structurally very similar to some elements of the neural network, and in the future, they can be used to modulate neuronal activity [32]. It has been found that carbon nanotubes can activate the electrical activity of neurons [33][34], suppress reactive astrogliosis [35], and modulate ion channel activity [36]. Selenium nanorods have, according to some parameters, more pronounced cytoprotective characteristics than spherical selenium nanoparticles.
Thus, despite a sufficient number of existing nanomaterials that can be used to prevent or treat strokes, there remain major problems in understanding the mechanisms of their action due to insufficient information on the dependence of the cytoprotective effectiveness of nanoparticles on their shape and size, and there are also limitations for a number of nanoparticles used in the form of their toxic effect on healthy organs and tissues. In this vein, nanoselenium has an undeniable priority, which is obtained from a vital microelement, selenium, which enters into the metabolism and acts through a separate class of proteins, selenoproteins and selenium-containing proteins, which will be discussed further.

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Subjects: Physiology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Egor A. Turovsky
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Alexey S. Baryshev
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Egor Y. Plotnikov
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Update Date: 29 Jan 2024
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