medlitГигиена и санитарияHygiene and Sanitation0016-99002412-0650Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0016-9900-2025-104-5-674-679gezijzmedlit-4938Research ArticleПРОФИЛАКТИЧЕСКАЯ ТОКСИКОЛОГИЯ И ГИГИЕНИЧЕСКОЕ НОРМИРОВАНИЕPREVENTIVE TOXICOLOGY AND HYGIENIC STANDARTIZATIONТоксикокинетика наночастиц в лёгких при хронической ингаляционной экспозиции (обзор литературы)Toxicokinetics of nanoparticles under chronic inhalation exposure (literature review)https://orcid.org/0000-0002-8284-0008ШабардинаЛада ВладимировнаShabardinaLada V.

Мл. науч. сотр. отд. токсикологии и биопрофилактики ФБУН «ЕМНЦ ПОЗРПП» Роспотребнадзора, 620014, Екатеринбург, Россия

e-mail: lada.shabardina@mail.ru

Junior researcher, Department of Toxicology and Bioprophylaxis, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: lada.shabardina@mail.ru

lada.shabardina@mail.ruhttps://orcid.org/0000-0002-4694-0175БатеневаВлада АндреевнаBatenevaVlada A.

Лаборант отд. токсикологии и биопрофилактики ФБУН «ЕМНЦ ПОЗРПП» Роспотребнадзора, 620014, Екатеринбург, Россия

e-mail: bateneva@ymrc.ru

Laboratory assistant of the Department of toxicology and bioprevention of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: bateneva@ymrc.ru

https://orcid.org/0000-0002-1743-7642СутунковаМарина ПетровнаSutunkovaMarina P.

Доктор мед. наук, директор ФБУН «ЕМНЦ ПОЗРПП» Роспотребнадзора, 620014, Екатеринбург, Россия

e-mail: sutunkova@ymrc.ru

DSc (Medicine), Director, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: sutunkova@ymrc.ru

sutunkova@ymrc.ruhttps://orcid.org/0000-0002-0097-7845МинигалиеваИльзира АмировнаMinigalievaIlzira A.

Доктор биол. наук, зав. отд. токсикологии и биопрофилактики ФБУН «ЕМНЦ ПОЗРПП» Роспотребнадзора, 620014, Екатеринбург, Россия

e-mail: ilzira@ymrc.ru

DSc (Medicine), Head of the Department of Toxicology and Bioprophylaxis, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: ilzira@ymrc.ru

ilzira@ymrc.ruhttps://orcid.org/0000-0003-0089-5177ФедотоваЛионэлла АйдыновнаFedotovaLionella A.

Канд. мед. наук, вед. науч. сотр. отд. токсикологии и биопрофилактики ФБУН «ЕМНЦ ПОЗРПП» Роспотребнадзора, 620014, Екатеринбург, Россия

e-mail: LFedotova@cspmz.ru

PhD (Medicine), leading Researcher Department of Toxicology and Bioprophylaxis, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: LFedotova@cspmz.ru

LFedotova@cspmz.ruФБУН «Екатеринбургский медицинский научный центр профилактики и охраны здоровья рабочих промпредприятий» РоспотребнадзораРоссияYekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial WorkersRussian FederationФБУН «Екатеринбургский медицинский научный центр профилактики и охраны здоровья рабочих промпредприятий» Роспотребнадзора; ФГБОУ ВО «Уральский государственный медицинский университет» Минздрава РоссииРоссияYekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers; Ural State Medical UniversityRussian FederationФБУН «Екатеринбургский медицинский научный центр профилактики и охраны здоровья рабочих промпредприятий» Роспотребнадзора; ФГБУ «Центр стратегического планирования и управления медико-биологическими рисками здоровью» ФМБА РоссииРоссияYekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers; Centre for Strategic Planning, of the Federal medical and biological agencyRussian Federation2025270620251045674679Copyright © Шабардина Л.В., Батенева В.А., Сутункова М.П., Минигалиева И.А., Федотова Л.А., 20252025Шабардина Л.В., Батенева В.А., Сутункова М.П., Минигалиева И.А., Федотова Л.А.Shabardina L.V., Bateneva V.A., Sutunkova M.P., Minigalieva I.A., Fedotova L.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rjhas.ru/jour/article/view/4938

Одним из важнейших аспектов оценки безопасности наноматериалов является определение их токсикокинетики и токсикодинамики. Известно, что наночастицы (НЧ) способны вызывать патофизиологические эффекты, проникая глубоко в ткани различных органов (особенно органов-мишеней, например, лёгких), однако закономерности их биораспределения ещё не изучены в полной мере.

Цель исследования – анализ источников современной научной литературы, посвящённой описанию основных путей поступления и распределения НЧ в лёгких млекопитающих при ингаляционном поступлении. Материалом для анализа послужили публикации за период с 2000 г. на русском и английском языке в изданиях, индексируемых в научных базах данных Scopus, Web of Science. Поиск осуществлялся с использованием PubMed, Google Scholar, eLIBRARY и CyberLeninka. Критерий исключения – работы, посвящённые токсикокинетике частиц более 100 нм. Поиск был ограничен рецензируемыми статьями, опубликованными с 2000 г. Установлено, что основной вклад в развитие и течение патологических процессов вносят уникальные физико-химические свойства НЧ, а также длительность экспозиции. Большую роль в распределении, выведении и депонировании поступивших в организм НЧ играют клетки иммунной системы, особенно макрофаги. Элиминация НЧ, как правило, происходит через мукоцилиарный эскалатор либо посредством фагоцитоза, либо транслокации в другие органы и ткани.

Заключение

Заключение. Необходимость дальнейших исследований закономерностей токсикинетики и токсикодинамики наночастиц обусловлена их многочисленными негативными эффектами, вызываемыми в живых системах.

Участие авторов

Участие авторов: Шабардина Л.В. – сбор материала, обработка данных, написание текста; Батенева В.А. – сбор материала и обработка данных; Сутункова М.П., Минигалиева И.А. – концепция и дизайн исследования, редактирование;Федотова Л.А. – редактирование. Все соавторы – утверждение окончательного варианта статьи, ответственность за целостность всех частей статьи.

Конфликт интересов

Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов в связи с публикацией данной статьи.

Финансирование

Финансирование. Исследование не имело финансовой поддержки.

Поступила

Поступила: 18.03.2025 / Принята к печати: 29.04.25 / Опубликована: 27.06.2025

The intensive use of nanomaterials and their unique physicochemical characteristics determine the relevance of establishing their effects on the body. Nanoparticles (NPs) are able to penetrate deep into the lungs causing pathophysiological response, but the patterns of their intrapulmonary biodistribution remain understudied. Our objective was to analyze recent publications describing the main routes of entry and pulmonary distribution of nanoparticles in mammals following inhalation exposure.

We analyzed scientific papers published in peer-reviewed journals since 2000, indexed in the Scopus and Web of Science databases, and found using PubMed, Google Scholar, eLibrary, and CyberLeninka. Studies of toxicokinetics of particles larger than 100 nm were not eligible for inclusion in the review.

We found unique physicochemical properties of nanoparticles and exposure duration to contribute the most to the development and course of pathological processes. Cells of the immune system, especially macrophages, play a major role in the distribution, clearance, and deposition of inhaled NPs. Elimination of nanoparticles usually occurs through the mucociliary escalator, either by phagocytosis or translocation to other organs and tissues.

Conclusion

Conclusion. A wide range of adverse effects of nanoparticles on living systems necessitates further research concerning the patterns of their toxicokinetics and toxicodynamics.

Contribution

Contribution: Shabardina L.V. – data collection and processing, draft manuscript preparation; Bateneva V.A. – data collection and processing; Sutunkova M.P., Minigalieva I.A. – study conception and design, editing; Fedotova L.A. – editing. All authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

Conflict of interest

Conflict of interest. The authors declare no conflict of interest.

Funding

Funding. The study had no sponsorship.

Received

Received: March 18, 2025 / Accepted: April 29, 2025 / Published: June 27, 2025

наночастицытоксикокинетикаингаляционное воздействиелёгочная тканьмакрофагиnanoparticlestoxicokineticsinhalation exposurelung tissuemacrophagesReferencesKhlebtsov N.G., Dykman L.A. Optical properties and biomedical applications of plasmonic nanoparticles. J. Quant. Spectrosc. Radiat. Transf. 2010; 111(1): 1–35. https://doi.org/10.1016/j.jqsrt.2009.07.012Khlebtsov N.G., Dykman L.A. Optical properties and biomedical applications of plasmonic nanoparticles. J. Quant. Spectrosc. Radiat. Transf. 2010; 111(1): 1–35. https://doi.org/10.1016/j.jqsrt.2009.07.012Zhang J.Z. Optical properties of metal oxide nanomaterials. In: Optical Properties and Spectroscopy of Nanomaterials. World Scientific; 2009: 181–203. https://doi.org/10.1142/9789812836663_0006Zhang J.Z. Optical properties of metal oxide nanomaterials. In: Optical Properties and Spectroscopy of Nanomaterials. World Scientific; 2009: 181–203. https://doi.org/10.1142/9789812836663_0006Khan I., Saeed K., Khan I. Nanoparticles: Properties, applications and toxicities. Arab. J. Chem. 2019; 12(7): 908–31. https://doi.org/10.1016/j.arabjc.2017.05.011Khan I., Saeed K., Khan I. Nanoparticles: Properties, applications and toxicities. Arab. J. Chem. 2019; 12(7): 908–31. https://doi.org/10.1016/j.arabjc.2017.05.011Oberdörster G., Oberdörster E., Oberdörster J. Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect. 2005; 113(7): 823–39. https://doi.org/10.1289/ehp.7339Oberdörster G., Oberdörster E., Oberdörster J. Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect. 2005; 113(7): 823–39. https://doi.org/10.1289/ehp.7339Lu X., Zhu T., Chen C., Liu Y. Right or left: the role of nanoparticles in pulmonary diseases. Int. J. Mol. Sci. 2014; 15(10): 17577–600. https://doi.org/10.3390/ijms151017577Lu X., Zhu T., Chen C., Liu Y. Right or left: the role of nanoparticles in pulmonary diseases. Int. J. Mol. Sci. 2014; 15(10): 17577–600. https://doi.org/10.3390/ijms151017577Hadrup N., Sørli J.B., Sharma A.K. Pulmonary toxicity, genotoxicity, and carcinogenicity evaluation of molybdenum, lithium, and tungsten: A review. Toxicology. 2022; 467: 153098. https://doi.org/10.1016/j.tox.2022.153098Hadrup N., Sørli J.B., Sharma A.K. Pulmonary toxicity, genotoxicity, and carcinogenicity evaluation of molybdenum, lithium, and tungsten: A review. Toxicology. 2022; 467: 153098. https://doi.org/10.1016/j.tox.2022.153098Johncy S.S., Dhanyakumar G., Samuel T.V., Ajay K.T., Bondade S.Y. Acute lung function response to dust in street sweepers. J. Clin. Diagn. Res. 2013; 7(10): 2126–9. https://doi.org/10.7860/JCDR/2013/5818.3449Johncy S.S., Dhanyakumar G., Samuel T.V., Ajay K.T., Bondade S.Y. Acute lung function response to dust in street sweepers. J. Clin. Diagn. Res. 2013; 7(10): 2126–9. https://doi.org/10.7860/JCDR/2013/5818.3449Srinivas A, Rao P.J., Selvam G., Murthy P.B., Reddy P.N. Acute inhalation toxicity of cerium oxide nanoparticles in rats. Toxicol. Lett. 2011; 205(2): 105–15. https://doi.org/10.1016/j.toxlet.2011.05.1027Srinivas A, Rao P.J., Selvam G., Murthy P.B., Reddy P.N. Acute inhalation toxicity of cerium oxide nanoparticles in rats. Toxicol. Lett. 2011; 205(2): 105–15. https://doi.org/10.1016/j.toxlet.2011.05.1027Marczynski M., Lieleg O. Forgotten but not gone: Particulate matter as contaminations of mucosal systems. Biophys. Rev. (Melville). 2021; 2(3): 031302. https://doi.org/10.1063/5.0054075Marczynski M., Lieleg O. Forgotten but not gone: Particulate matter as contaminations of mucosal systems. Biophys. Rev. (Melville). 2021; 2(3): 031302. https://doi.org/10.1063/5.0054075Braakhuis H.M., Park M.V., Gosens I., De Jong W.H., Cassee F.R. Physicochemical characteristics of nanomaterials that affect pulmonary inflammation. Part. Fibre Toxicol. 2014; 11: 18. https://doi.org/10.1186/1743-8977-11-18Braakhuis H.M., Park M.V., Gosens I., De Jong W.H., Cassee F.R. Physicochemical characteristics of nanomaterials that affect pulmonary inflammation. Part. Fibre Toxicol. 2014; 11: 18. https://doi.org/10.1186/1743-8977-11-18Ross M.H., Pawlina W. Histology: A Text and Atlas with Correlated Cell and Molecular Biology. Lippincott Williams & Wilkins; 2016.Ross M.H., Pawlina W. Histology: A Text and Atlas with Correlated Cell and Molecular Biology. Lippincott Williams & Wilkins; 2016.Горбачева Н.В., Кулич Н.В., Кузьмина Н.Д. Учет дисперсного состава вдыхаемой фракции и закономерностей аккумуляции аэрозоля в различных отделах дыхательного тракта при расчете доз внутреннего облучения. Вестник Университета гражданской защиты МЧС Беларуси. 2017; 1(3): 291–8. https://doi.org/10.33408/2519-237X.2017.1-3.291 https://elibrary.ru/zfovktHarbacheva N.V., Kulich N.V., Kuzmina N.D. Accounting of the dispersed composition of the intraflaced fraction and the regularities of aerosol’s accumulation in various deposits of the respiratory tract when calculating doses of internal irradiation. Vestnik Universiteta grazhdanskoi zashchity MCHS Belarusi. 2017; 1(3): 291–8. https://doi.org/10.33408/2519-237X.2017.1-3.291 https://elibrary.ru/zfovkt (in Russian)Wang L., Wang L., Ding W., Zhang F. Acute toxicity of ferric oxide and zinc oxide nanoparticles in rats. J. Nanosci. Nanotechnol. 2010; 10(12): 8617–24. https://doi.org/10.1166/jnn.2010.2483Wang L., Wang L., Ding W., Zhang F. Acute toxicity of ferric oxide and zinc oxide nanoparticles in rats. J. Nanosci. Nanotechnol. 2010; 10(12): 8617–24. https://doi.org/10.1166/jnn.2010.2483Liu Q., Zhang X., Xue J., Chai J., Qin L., Guan J., et al. Exploring the intrinsic micro-/nanoparticle size on their in vivo fate after lung delivery. J. Control. Release. 2022; 347: 435–48. https://doi.org/10.1016/j.jconrel.2022.05.006Liu Q., Zhang X., Xue J., Chai J., Qin L., Guan J., et al. Exploring the intrinsic micro-/nanoparticle size on their in vivo fate after lung delivery. J. Control. Release. 2022; 347: 435–48. https://doi.org/10.1016/j.jconrel.2022.05.006Schuster B.S., Suk J.S., Woodworth G.F., Hanes J. Nanoparticle diffusion in respiratory mucus from humans without lung disease. Biomaterials. 2013; 34(13): 3439–46. https://doi.org/10.1016/j.biomaterials.2013.01.064Schuster B.S., Suk J.S., Woodworth G.F., Hanes J. Nanoparticle diffusion in respiratory mucus from humans without lung disease. Biomaterials. 2013; 34(13): 3439–46. https://doi.org/10.1016/j.biomaterials.2013.01.064Braakhuis H.M., Gosens I., Krystek P., Boere J.A.F., Cassee F.R., Fokkens P.H.B., et al. Particle size dependent deposition and pulmonary inflammation after short-term inhalation of silver nanoparticles. Part. Fibre Toxicol. 2014; 11: 49. https://doi.org/10.1186/s12989-014-0049-1Braakhuis H.M., Gosens I., Krystek P., Boere J.A.F., Cassee F.R., Fokkens P.H.B., et al. Particle size dependent deposition and pulmonary inflammation after short-term inhalation of silver nanoparticles. Part. Fibre Toxicol. 2014; 11: 49. https://doi.org/10.1186/s12989-014-0049-1Jachak A., Lai K.S., Hida K., Suk J.S., Markovic N., Biswal S., et al. Transport of metal oxide nanoparticles and single-walled carbon nanotubes in human mucus. Nanotoxicology. 2012; 6(6): 614–22. https://doi.org/10.3109/17435390.2011.598244Jachak A., Lai K.S., Hida K., Suk J.S., Markovic N., Biswal S., et al. Transport of metal oxide nanoparticles and single-walled carbon nanotubes in human mucus. Nanotoxicology. 2012; 6(6): 614–22. https://doi.org/10.3109/17435390.2011.598244Fujihara J., Nishimoto N. Review of zinc oxide nanoparticles: Toxicokinetics, tissue distribution for various exposure routes, toxicological effects, toxicity mechanism in mammals, and an approach for toxicity reduction. Biol. Trace Elem. Res. 2023; 202(1): 9–23. https://doi.org/10.1007/s12011-023-03644-wFujihara J., Nishimoto N. Review of zinc oxide nanoparticles: Toxicokinetics, tissue distribution for various exposure routes, toxicological effects, toxicity mechanism in mammals, and an approach for toxicity reduction. Biol. Trace Elem. Res. 2023; 202(1): 9–23. https://doi.org/10.1007/s12011-023-03644-wLieleg O., Vladescu I., Ribbeck K. Characterization of particle translocation through mucin hydrogels. Biophys. J. 2010; 98(9): 1782–9. https://doi.org/10.1016/j.bpj.2010.01.012Lieleg O., Vladescu I., Ribbeck K. Characterization of particle translocation through mucin hydrogels. Biophys. J. 2010; 98(9): 1782–9. https://doi.org/10.1016/j.bpj.2010.01.012Li L.D., Crouzier T., Sarkar A., Dunphy L., Han J., Ribbeck K. Spatial configuration and composition of charge modulates transport into a mucin hydrogel barrier. Biophys. J. 2013; 105(6): 1357–65. https://doi.org/10.1016/j.bpj.2013.07.050Li L.D., Crouzier T., Sarkar A., Dunphy L., Han J., Ribbeck K. Spatial configuration and composition of charge modulates transport into a mucin hydrogel barrier. Biophys. J. 2013; 105(6): 1357–65. https://doi.org/10.1016/j.bpj.2013.07.050Xu Y.M., Tan H.W., Zheng W., Liang Z.L., Yu F.Y., Wu D.D., et al. Cadmium telluride quantum dot-exposed human bronchial epithelial cells: A further study of the cellular response by proteomics. Toxicol. Res. (Camb.). 2019; 8(6): 994–1001. https://doi.org/10.1039/c9tx00126cXu Y.M., Tan H.W., Zheng W., Liang Z.L., Yu F.Y., Wu D.D., et al. Cadmium telluride quantum dot-exposed human bronchial epithelial cells: A further study of the cellular response by proteomics. Toxicol. Res. (Camb.). 2019; 8(6): 994–1001. https://doi.org/10.1039/c9tx00126cGeiser M., Casaulta M., Kupferschmid B., Schulz H., Semmler-Behnke M., Kreyling W. The role of macrophages in the clearance of inhaled ultrafine titanium dioxide particles. Am. J. Respir. Cell Mol. Biol. 2008; 38(3): 371–6. https://doi.org/10.1165/rcmb.2007-0138OCGeiser M., Casaulta M., Kupferschmid B., Schulz H., Semmler-Behnke M., Kreyling W. The role of macrophages in the clearance of inhaled ultrafine titanium dioxide particles. Am. J. Respir. Cell Mol. Biol. 2008; 38(3): 371–6. https://doi.org/10.1165/rcmb.2007-0138OCGeiser M., Rothen-Rutishauser B., Kapp N., Schürch S.N., Kreyling W., Schulz H., et al. Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells. Environ. Health Perspect. 2005; 113(11): 1555–60. https://doi.org/10.1289/ehp.8006Geiser M., Rothen-Rutishauser B., Kapp N., Schürch S.N., Kreyling W., Schulz H., et al. Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells. Environ. Health Perspect. 2005; 113(11): 1555–60. https://doi.org/10.1289/ehp.8006Kim Y.H., Fazlollahi F., Kennedy I.M., Yacobi N.R., Hamm-Alvarez S.F., Borok Z., et al. Alveolar epithelial cell injury due to zinc oxide nanoparticle exposure. Am. J. Respir. Crit. Care Med. 2010; 182(11): 1398–409. https://doi.org/10.1164/rccm.201002-0185OCKim Y.H., Fazlollahi F., Kennedy I.M., Yacobi N.R., Hamm-Alvarez S.F., Borok Z., et al. Alveolar epithelial cell injury due to zinc oxide nanoparticle exposure. Am. J. Respir. Crit. Care Med. 2010; 182(11): 1398–409. https://doi.org/10.1164/rccm.201002-0185OCLipka J., Semmler-Behnke M., Sperling R.A., Wenk A., Takenaka S., Schleh C., et al. Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection. Biomaterials. 2010; 31(25): 6574–81. https://doi.org/10.1016/j.biomaterials.2010.05.009Lipka J., Semmler-Behnke M., Sperling R.A., Wenk A., Takenaka S., Schleh C., et al. Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection. Biomaterials. 2010; 31(25): 6574–81. https://doi.org/10.1016/j.biomaterials.2010.05.009Shah P., Lalan M., Jani D. Toxicological aspects of carbon nanotubes, fullerenes and graphenes. Curr. Pharm. Des. 2021; 27(4): 556–64. https://doi.org/10.2174/1381612826666200916143741Shah P., Lalan M., Jani D. Toxicological aspects of carbon nanotubes, fullerenes and graphenes. Curr. Pharm. Des. 2021; 27(4): 556–64. https://doi.org/10.2174/1381612826666200916143741Vysloužil J., Kulich P., Zeman T., Vaculovič T., Tvrdoňová M., Mikuška P., et al. Subchronic continuous inhalation exposure to zinc oxide nanoparticles induces pulmonary cell response in mice. J. Trace Elem. Med. Biol. 2020; 61: 126511. https://doi.org/10.1016/j.jtemb.2020.126511Vysloužil J., Kulich P., Zeman T., Vaculovič T., Tvrdoňová M., Mikuška P., et al. Subchronic continuous inhalation exposure to zinc oxide nanoparticles induces pulmonary cell response in mice. J. Trace Elem. Med. Biol. 2020; 61: 126511. https://doi.org/10.1016/j.jtemb.2020.126511Cai D., Gao W., Li Z., Zhang Y., Xiao L., Xiao Y. Current development of nano-drug delivery to target macrophages. Biomedicines. 2022; 10(5): 1203. https://doi.org/10.3390/biomedicines10051203Cai D., Gao W., Li Z., Zhang Y., Xiao L., Xiao Y. Current development of nano-drug delivery to target macrophages. Biomedicines. 2022; 10(5): 1203. https://doi.org/10.3390/biomedicines10051203Pauluhn J. Poorly soluble particulates: searching for a unifying denominator of nanoparticles and fine particles for DNEL estimation. Toxicology. 2011; 279(1–3): 176–88. https://doi.org/10.1016/j.tox.2010.10.009Pauluhn J. Poorly soluble particulates: searching for a unifying denominator of nanoparticles and fine particles for DNEL estimation. Toxicology. 2011; 279(1–3): 176–88. https://doi.org/10.1016/j.tox.2010.10.009Molina R.M., Konduru N.V., Queiroz P.M., Figueroa B., Fu D., Ma-Hock L., et al. Fate of barium sulfate nanoparticles deposited in the lungs of rats. Sci. Rep. 2019; 9(1): 8163. https://doi.org/10.1038/s41598-019-44551-2Molina R.M., Konduru N.V., Queiroz P.M., Figueroa B., Fu D., Ma-Hock L., et al. Fate of barium sulfate nanoparticles deposited in the lungs of rats. Sci. Rep. 2019; 9(1): 8163. https://doi.org/10.1038/s41598-019-44551-2Лаберко Е.Л., Богомильский М.Р. Современные представления о регуляции мукоцилиарного клиренса (обзор литературы). Вестник Российского государственного медицинского университета. 2015; (1): 60–4. https://elibrary.ru/ulxxrpLaberko E.L., Bogomilskiy M.R. Modern view on mucociliary clearance regulation: A literature review. Vestnik Rossiiskogo gosudarstvennogo meditsinskogo universiteta. 2015; (1): 60–4. https://elibrary.ru/ulxxrp (in Russian)Johncy S.S., Dhanyakumar G., Kanyakumari K., Samuel T.V. Chronic exposure to dust and lung function impairment: A study on female sweepers in India. Natl. J. Physiol. Pharm. Pharmacol. 2014; 4(1): 15–9. https://doi.org/10.5455/njppp.2014.4.140620131Johncy S.S., Dhanyakumar G., Kanyakumari K., Samuel T.V. Chronic exposure to dust and lung function impairment: A study on female sweepers in India. Natl. J. Physiol. Pharm. Pharmacol. 2014; 4(1): 15–9. https://doi.org/10.5455/njppp.2014.4.140620131Jin J., Zhou K.K., Park K., Hu Y., Xu X., Zheng Z., et al. Anti-inflammatory and antiangiogenic effects of nanoparticle-mediated delivery of a natural angiogenic inhibitor. Invest. Ophthalmol. Vis. Sci. 2011; 52(9): 6230–7. https://doi.org/10.1167/iovs.10-6229Jin J., Zhou K.K., Park K., Hu Y., Xu X., Zheng Z., et al. Anti-inflammatory and antiangiogenic effects of nanoparticle-mediated delivery of a natural angiogenic inhibitor. Invest. Ophthalmol. Vis. Sci. 2011; 52(9): 6230–7. https://doi.org/10.1167/iovs.10-6229Geiser M., Kreyling W.G. Deposition and biokinetics of inhaled nanoparticles. Part. Fibre Toxicol. 2010; 7: 2. https://doi.org/10.1186/1743-8977-7-2Geiser M., Kreyling W.G. Deposition and biokinetics of inhaled nanoparticles. Part. Fibre Toxicol. 2010; 7: 2. https://doi.org/10.1186/1743-8977-7-2Kirch J., Guenther M., Doshi N., Schaefer U.F., Schneider M., Mitragotri S., et al. Mucociliary clearance of micro- and nanoparticles is independent of size, shape and charge – an ex vivo and in silico approach. J. Control. Release. 2012; 159(1): 128–34. https://doi.org/10.1016/j.jconrel.2011.12.015Kirch J., Guenther M., Doshi N., Schaefer U.F., Schneider M., Mitragotri S., et al. Mucociliary clearance of micro- and nanoparticles is independent of size, shape and charge – an ex vivo and in silico approach. J. Control. Release. 2012; 159(1): 128–34. https://doi.org/10.1016/j.jconrel.2011.12.015Blank F., Rothen-Rutishauser B., Gehr P. Dendritic cells and macrophages form a transepithelial network against foreign particulate antigens. Am. J. Respir. Cell Mol. Biol. 2007; 36(6): 669–77. https://doi.org/10.1165/rcmb.2006-0234OCBlank F., Rothen-Rutishauser B., Gehr P. Dendritic cells and macrophages form a transepithelial network against foreign particulate antigens. Am. J. Respir. Cell Mol. Biol. 2007; 36(6): 669–77. https://doi.org/10.1165/rcmb.2006-0234OCAreecheewakul S., Adamcakova-Dodd A., Haque E., Jing X., Meyerholz D.K., O’Shaughnessy P.T., et al. Time course of pulmonary inflammation and trace element biodistribution during and after sub-acute inhalation exposure to copper oxide nanoparticles in a murine model. Part. Fibre Toxicol. 2022; 19(1): 40. https://doi.org/10.1186/s12989-022-00480-zAreecheewakul S., Adamcakova-Dodd A., Haque E., Jing X., Meyerholz D.K., O’Shaughnessy P.T., et al. Time course of pulmonary inflammation and trace element biodistribution during and after sub-acute inhalation exposure to copper oxide nanoparticles in a murine model. Part. Fibre Toxicol. 2022; 19(1): 40. https://doi.org/10.1186/s12989-022-00480-zSacks D., Baxter B., Campbell B.C.V., Carpenter J.S., Cognard C., Dippel D., et al. Multisociety consensus quality improvement revised consensus statement for endovascular therapy of acute ischemic stroke. Int. J. Stroke. 2018; 13(6): 612–32. https://doi.org/10.1177/1747493018778713Sacks D., Baxter B., Campbell B.C.V., Carpenter J.S., Cognard C., Dippel D., et al. Multisociety consensus quality improvement revised consensus statement for endovascular therapy of acute ischemic stroke. Int. J. Stroke. 2018; 13(6): 612–32. https://doi.org/10.1177/1747493018778713Blanco E., Shen H., Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 2015; 33(9): 941–51. https://doi.org/10.1038/nbt.3330Blanco E., Shen H., Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 2015; 33(9): 941–51. https://doi.org/10.1038/nbt.3330Du B., Jiang X., Das A., Zhou Q., Yu M., Jin R., et al. Glomerular barrier behaves as an atomically precise bandpass filter in a sub-nanometre regime. Nat. Nanotechnol. 2017; 12(11): 1096–102. https://doi.org/10.1038/nnano.2017.170Du B., Jiang X., Das A., Zhou Q., Yu M., Jin R., et al. Glomerular barrier behaves as an atomically precise bandpass filter in a sub-nanometre regime. Nat. Nanotechnol. 2017; 12(11): 1096–102. https://doi.org/10.1038/nnano.2017.170Choi H.S., Liu W., Misra P., Tanaka E., Zimmer J.P., Itty Ipe B., et al. Renal clearance of quantum dots. Nat. Biotechnol. 2007; 25(10): 1165–70. https://doi.org/10.1038/nbt1340Choi H.S., Liu W., Misra P., Tanaka E., Zimmer J.P., Itty Ipe B., et al. Renal clearance of quantum dots. Nat. Biotechnol. 2007; 25(10): 1165–70. https://doi.org/10.1038/nbt1340Sun T., Zhang Y.S., Pang B., Hyun D.C., Yang M., Xia Y. Engineered nanoparticles for drug delivery in cancer therapy. Angew. Chem. Int. Ed. Engl. 2014; 53(46): 12320–64. https://doi.org/10.1002/anie.201403036Sun T., Zhang Y.S., Pang B., Hyun D.C., Yang M., Xia Y. Engineered nanoparticles for drug delivery in cancer therapy. Angew. Chem. Int. Ed. Engl. 2014; 53(46): 12320–64. https://doi.org/10.1002/anie.201403036de Barros A.B., Tsourkas A., Saboury B., Cardoso V.N., Alavi A. Emerging role of radiolabeled nanoparticles as an effective diagnostic technique. EJNMMI Res. 2012; 2(1): 39. https://doi.org/10.1186/2191-219X-2-39de Barros A.B., Tsourkas A., Saboury B., Cardoso V.N., Alavi A. Emerging role of radiolabeled nanoparticles as an effective diagnostic technique. EJNMMI Res. 2012; 2(1): 39. https://doi.org/10.1186/2191-219X-2-39Du B., Yu M., Zheng J. Transport and interactions of nanoparticles in the kidneys. Nat. Rev. Mater. 2018; 3(10): 358–74. https://doi.org/10.1038/s41578-018-0038-3Du B., Yu M., Zheng J. Transport and interactions of nanoparticles in the kidneys. Nat. Rev. Mater. 2018; 3(10): 358–74. https://doi.org/10.1038/s41578-018-0038-3Schneider T., Mittag A., Westermann M., Glei M. Impact of pH changes on metal oxide nanoparticle behaviour during artificial digestion. Food Funct. 2021; 12(4): 1452–7. https://doi.org/10.1039/d0fo02842hSchneider T., Mittag A., Westermann M., Glei M. Impact of pH changes on metal oxide nanoparticle behaviour during artificial digestion. Food Funct. 2021; 12(4): 1452–7. https://doi.org/10.1039/d0fo02842hLaloux L., Kastrati D., Cambier S., Gutleb A.C., Schneider Y.J. The food matrix and the gastrointestinal fluids alter the features of silver nanoparticles. Small. 2020; 16(21): e1907687. https://doi.org/10.1002/smll.201907687Laloux L., Kastrati D., Cambier S., Gutleb A.C., Schneider Y.J. The food matrix and the gastrointestinal fluids alter the features of silver nanoparticles. Small. 2020; 16(21): e1907687. https://doi.org/10.1002/smll.201907687De Jong W.H., De Rijk E., Bonetto A., Wohlleben W., Stone V., Brunelli A., et al. Toxicity of copper oxide and basic copper carbonate nanoparticles after short-term oral exposure in rats. Nanotoxicology. 2019; 13(1): 50–72. https://doi.org/10.1080/17435390.2018.1530390De Jong W.H., De Rijk E., Bonetto A., Wohlleben W., Stone V., Brunelli A., et al. Toxicity of copper oxide and basic copper carbonate nanoparticles after short-term oral exposure in rats. Nanotoxicology. 2019; 13(1): 50–72. https://doi.org/10.1080/17435390.2018.1530390Sinnecker H., Krause T., Koelling S., Lautenschläger I., Frey A. The gut wall provides an effective barrier against nanoparticle uptake. Beilstein J. Nanotechnol. 2014; 5: 2092–101. https://doi.org/10.3762/bjnano.5.218Sinnecker H., Krause T., Koelling S., Lautenschläger I., Frey A. The gut wall provides an effective barrier against nanoparticle uptake. Beilstein J. Nanotechnol. 2014; 5: 2092–101. https://doi.org/10.3762/bjnano.5.218Bredeck G., Kämpfer A.A.M., Sofranko A., Wahle T., Büttner V., Albrecht C., et al. Ingested engineered nanomaterials affect the expression of mucin genes – an in vitro – in vivo comparison. Nanomaterials (Basel). 2021; 11(10): 2621. https://doi.org/10.3390/nano11102621Bredeck G., Kämpfer A.A.M., Sofranko A., Wahle T., Büttner V., Albrecht C., et al. Ingested engineered nanomaterials affect the expression of mucin genes – an in vitro – in vivo comparison. Nanomaterials (Basel). 2021; 11(10): 2621. https://doi.org/10.3390/nano11102621Bae S.H., Yu J., Go M.R., Kim H.J., Hwang Y.G., Choi S.J. Oral toxicity and intestinal transport mechanism of colloidal gold nanoparticle-treated red ginseng. Nanomaterials (Basel). 2016; 6(11): 208. https://doi.org/10.3390/nano6110208Bae S.H., Yu J., Go M.R., Kim H.J., Hwang Y.G., Choi S.J. Oral toxicity and intestinal transport mechanism of colloidal gold nanoparticle-treated red ginseng. Nanomaterials (Basel). 2016; 6(11): 208. https://doi.org/10.3390/nano6110208

The authors declare that there are no conflicts of interest present.