Mechanisms of cellular protection against nanomaterials

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Abstract

Introduction. Entry of inorganic and organic nanomaterials through respiratory tract, skin and digestive system increases the risks of immunological disorders, hereditary and oncological diseases. Localization and stability of nanoparticles are determined by the mechanisms of inter- and intracellular vesicular transport.

The aim. Study of cellular uptake, targeted intracellular delivery, degradation and secretion of nanomaterials on the base of mechanisms of vesicular transport, unspecific innate resistance and adaptive immune response.

Results. Physical and chemical properties of nanomaterials determine their high reactivity and economy, penetration into organisms through all protective barriers and in any cells by means of endocytosis, macropinocytosis and phagocytosis. Concerns related to nanotechnology development include risks of: 1) cytotoxicity of nanomaterials, products of their cellular metabolism and delivered materials in nanocarriers; 2) immunological disorders resulted from immune status disbalance, chronic inflammation, allergic and autoimmune complications. Endocytosis and phagocytosis of nanomaterials cause destruction of foreign substances in lysosomes and secretion of free nanoparticles, extracellular vesicules and lysosomes containing nanoparticles. For intercellular exchange tunneling nanotubes are formed. Neutrophil extracellular traps provide barrier functions and deposition. Protection of organisms includes phagocytosis of nanomaterials, their detoxication in liver and spleen with subsequent excretion, and unspecific innate resistance with cytokine gene expression.

Conclusion. Natural mechanisms of cellular protection are based on nanoparticle degradation in lysosomes, secretion of foreign materials in free form, as part of extracellular vesicles or lysosomes, formation of tunneling nanotubes and neutrophil extracellular traps. Besides, antigen presentation causes cytokine gene expression resulting in protective reactions of organism.

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About the authors

Olga V. Morozova

Federal Research Clinical Center of Physical-Chemical Medicine named after Yu.M. Lopukhin of the Federal Medical and Biological Agency of Russia; National Research Center of Epidemiology and Microbiology of N.F. Gamaleya of the Russian Ministry of Health, Gamaleya Street 16, Moscow, 123098; Sirius University of Science and Technology

Author for correspondence.
Email: omorozova2010@gmail.com
ORCID iD: 0000-0001-9630-0777

leading researcer, doctor of Sciences

Russian Federation, Malaya Pirogovskaya Street 1а, Moscow, 119435; Gamaleya Street 16, Moscow, 123098; 1, Olympic Ave., Sochi, 354349

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Supplementary files

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1. JATS XML
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2. Fig. 1. Scheme of 4 types of endocytosis, including clathrin- and caveolin-mediated endocytosis, phagocytosis, macropinocytosis and pinocytosis, and nanoparticle exocytosis [10]

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3. Fig. 2. Accumulation dynamics of fluorescent protein nanoparticles after oral administration in different parts of rabbit brain

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4. Fig. 3. Scheme of intercellular transfer of mitochondria from a mesenchymal stromal cell to a damaged cell and a transmission electron microscopy (TEM) image of a tunneling nanotube [1]

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