{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:01:56Z","timestamp":1790402516109,"version":"4.1.0"},"reference-count":82,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Austrian Ministry of Defense (BMLV)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>As common industrial by-products, airborne engineered nanomaterials are considered important environmental toxins to monitor due to their potential health risks to humans and animals. The main uptake routes of airborne nanoparticles are nasal and\/or oral inhalation, which are known to enable the transfer of nanomaterials into the bloodstream resulting in the rapid distribution throughout the human body. Consequently, mucosal barriers present in the nose, buccal, and lung have been identified and intensively studied as the key tissue barrier to nanoparticle translocation. Despite decades of research, surprisingly little is known about the differences among various mucosa tissue types to tolerate nanoparticle exposures. One limitation in comparing nanotoxicological data sets can be linked to a lack of harmonization and standardization of cell-based assays, where (a) different cultivation conditions such as an air-liquid interface or submerged cultures, (b) varying barrier maturity, and (c) diverse media substitutes have been used. The current comparative nanotoxicological study, therefore, aims at analyzing the toxic effects of nanomaterials on four human mucosa barrier models including nasal (RPMI2650), buccal (TR146), alveolar (A549), and bronchial (Calu-3) mucosal cell lines to better understand the modulating effects of tissue maturity, cultivation conditions, and tissue type using standard transwell cultivations at liquid-liquid and air-liquid interfaces. Overall, cell size, confluency, tight junction localization, and cell viability as well as barrier formation using 50% and 100% confluency was monitored using trans-epithelial-electrical resistance (TEER) measurements and resazurin-based Presto Blue assays of immature (e.g., 5 days) and mature (e.g., 22 days) cultures in the presence and absence of corticosteroids such as hydrocortisone. Results of our study show that cellular viability in response to increasing nanoparticle exposure scenarios is highly compound and cell-type specific (TR146 6 \u00b1 0.7% at 2 mM ZnO (ZnO) vs. ~90% at 2 mM TiO2 (TiO2) for 24 h; Calu3 93.9 \u00b1 4.21% at 2 mM ZnO vs. ~100% at 2 mM TiO2). Nanoparticle-induced cytotoxic effects under air-liquid cultivation conditions declined in RPMI2650, A549, TR146, and Calu-3 cells (~0.7 to ~0.2-fold), with increasing 50 to 100% barrier maturity under the influence of ZnO (2 mM). Cell viability in early and late mucosa barriers where hardly influenced by TiO2 as well as most cell types did not fall below 77% viability when added to Individual ALI cultures. Fully maturated bronchial mucosal cell barrier models cultivated under ALI conditions showed less tolerance to acute ZnO nanoparticle exposures (~50% remaining viability at 2 mM ZnO for 24 h) than the similarly treated but more robust nasal (~74%), buccal (~73%), and alveolar (~82%) cell-based models.<\/jats:p>","DOI":"10.3390\/ijms24065634","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T03:50:45Z","timestamp":1678938645000},"page":"5634","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Cultivation Modality and Barrier Maturity Modulate the Toxicity of Industrial Zinc Oxide and Titanium Dioxide Nanoparticles on Nasal, Buccal, Bronchial, and Alveolar Mucosa Cell-Derived Barrier Models"],"prefix":"10.3390","volume":"24","author":[{"given":"Helene","family":"Stuetz","sequence":"first","affiliation":[{"name":"Faculty of Technical Chemistry, Institute of Applied Synthetic Chemistry and Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9\/163-164, 1060 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6614-7369","authenticated-orcid":false,"given":"Eva I.","family":"Reihs","sequence":"additional","affiliation":[{"name":"Faculty of Technical Chemistry, Institute of Applied Synthetic Chemistry and Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9\/163-164, 1060 Vienna, Austria"},{"name":"Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-22, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6552-7183","authenticated-orcid":false,"given":"Winfried","family":"Neuhaus","sequence":"additional","affiliation":[{"name":"Competence Unit Molecular Diagnostics, Center Health and Bioresources, AIT Austrian Institute of Technology GmbH, Giefinggasse 4, 1210 Vienna, Austria"},{"name":"Department of Medicine, Faculty of Medicine and Dentistry, Danube Private University, 3500 Krems an der Donau, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maren","family":"Pfl\u00fcger","sequence":"additional","affiliation":[{"name":"Medical and Pharmaceutical Biotechnology, IMC University of Applied Sciences, Am Campus Krems, Trakt G, 3500 Krems an der Donau, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Hundsberger","sequence":"additional","affiliation":[{"name":"Medical and Pharmaceutical Biotechnology, IMC University of Applied Sciences, Am Campus Krems, Trakt G, 3500 Krems an der Donau, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Ertl","sequence":"additional","affiliation":[{"name":"Faculty of Technical Chemistry, Institute of Applied Synthetic Chemistry and Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9\/163-164, 1060 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Resch","sequence":"additional","affiliation":[{"name":"Science, Research, and Development Division, Austrian Federal Ministry of Defence, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Bauer","sequence":"additional","affiliation":[{"name":"Science, Research, and Development Division, Austrian Federal Ministry of Defence, 1090 Vienna, Austria"},{"name":"CBRN-Defence-Centre, Austrian Armed Forces, 2100 Korneuburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnter","family":"Povoden","sequence":"additional","affiliation":[{"name":"CBRN-Defence-Centre, Austrian Armed Forces, 2100 Korneuburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9928-3631","authenticated-orcid":false,"given":"Mario","family":"Rothbauer","sequence":"additional","affiliation":[{"name":"Faculty of Technical Chemistry, Institute of Applied Synthetic Chemistry and Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9\/163-164, 1060 Vienna, Austria"},{"name":"Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-22, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"376","DOI":"10.12688\/f1000research.12691.1","article-title":"Hazard and risk assessment strategies for nanoparticle exposures: How far have we come in the past 10 years?","volume":"7","author":"Warheit","year":"2018","journal-title":"F1000Research"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1016\/j.apt.2021.03.033","article-title":"Uncertainty assessment for the airborne nanoparticle collection efficiency of a TEM grid-equipped sampling system by Monte-Carlo calculation","volume":"32","author":"Xiang","year":"2021","journal-title":"Adv. Powder Technol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1080\/02786826.2020.1870923","article-title":"Airborne nanoparticle collection efficiency of a TEM grid-equipped sampling system","volume":"55","author":"Xiang","year":"2021","journal-title":"Aerosol Sci. Technol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"185080","DOI":"10.1155\/2014\/185080","article-title":"Evaluation of the Particle Aerosolization from n-TiO2Photocatalytic Nanocoatings under Abrasion","volume":"2014","author":"Shandilya","year":"2014","journal-title":"J. Nanomater."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"931405","DOI":"10.1155\/2015\/931405","article-title":"Exposure Assessment Based Recommendations to Improve Nanosafety at Nanoliposome Production Sites","volume":"2015","author":"Bressot","year":"2015","journal-title":"J. Nanomater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1177\/0954407021993011","article-title":"Representativeness of airborne brake wear emission for the automotive industry: A review","volume":"235","author":"Philippe","year":"2021","journal-title":"Proc. Inst. Mech. Eng. Part D J. Automob. Eng."},{"key":"ref_7","first-page":"239784732097778","article-title":"Emission rate assessment of airborne brake particles by characterization of the pad and disc surfaces from a pin-on-disc tribometer","volume":"4","author":"Philippe","year":"2020","journal-title":"Toxicol. Res. Appl."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"De Matteis, V. (2017). Exposure to Inorganic Nanoparticles: Routes of Entry, Immune Response, Biodistribution and In Vitro\/In Vivo Toxicity Evaluation. Toxics, 5.","DOI":"10.3390\/toxics5040029"},{"key":"ref_9","first-page":"337","article-title":"Deposition, retention, and clearance of inhaled particles","volume":"37","author":"Lippmann","year":"1980","journal-title":"Br. J. Ind. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100125","DOI":"10.1016\/j.envadv.2021.100125","article-title":"Airborne particulate matter in an iron mining city: Characterization, cell uptake and cytotoxicity effects of nanoparticles from PM2.5, PM10 and PM20 on human lung cells","volume":"6","author":"Morozesk","year":"2021","journal-title":"Environ. Adv."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wang, S., Alenius, H., El-Nezami, H., and Karisola, P. (2022). A New Look at the Effects of Engineered ZnO and TiO2 Nanoparticles: Evidence from Transcriptomics Studies. Nanomaterials, 12.","DOI":"10.3390\/nano12081247"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"102092","DOI":"10.1016\/j.redox.2021.102092","article-title":"Oxidant-induced epithelial alarmin pathway mediates lung inflammation and functional decline following ultrafine carbon and ozone inhalation co-exposure","volume":"46","author":"Majumder","year":"2021","journal-title":"Redox Biol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Salvador, A., Katsumiti, A., Rojas, E., Aristimu\u00f1o, C., Betanzos, M., Mart\u00ednez-Moro, M., Moya, S.E., and Go\u00f1i-De-cerio, F. (2021). A complete in vitro toxicological assessment of the biological effects of cerium oxide nanoparticles: From acute toxicity to multi-dose subchronic cytotoxicity study. Nanomaterials, 11.","DOI":"10.20944\/preprints202105.0522.v1"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Di Giampaolo, L., Zaccariello, G., Benedetti, A., Vecchiotti, G., Caposano, F., Sabbioni, E., Groppi, F., Manenti, S., Niu, Q., and Maria, A. (2021). Genotoxicity and Immunotoxicity of Titanium Dioxide-Embedded Mesoporous Silica Nanoparticles (TiO2@MSN) in Primary Peripheral Human Blood Mononuclear Cells (PBMC). Nanomaterials, 11.","DOI":"10.3390\/nano11020270"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"61","DOI":"10.2147\/NSA.S23932","article-title":"A review of mammalian toxicity of ZnO nanoparticles","volume":"5","author":"Vandebriel","year":"2012","journal-title":"Nanotechnol. Sci. Appl."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"762","DOI":"10.2174\/1389557516666160321114341","article-title":"Titanium Dioxide Nanoparticles: A Risk for Human Health?","volume":"16","author":"Grande","year":"2016","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/smll.201201363","article-title":"Exposure to Titanium Dioxide Nanoparticles Induces Autophagy in Primary Human Keratinocytes","volume":"9","author":"Zhao","year":"2013","journal-title":"Small"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s12011-010-8707-0","article-title":"Cellular toxicity of TiO2 nanoparticles in anatase and rutile crystal phase","volume":"141","author":"Jin","year":"2011","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e549","DOI":"10.1038\/cddis.2013.76","article-title":"Metabolic effects of TiO2 nanoparticles, a common component of sunscreens and cosmetics, on human keratinocytes","volume":"4","author":"Tucci","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s11671-017-2242-2","article-title":"The Potential Liver, Brain, and Embryo Toxicity of Titanium Dioxide Nanoparticles on Mice","volume":"12","author":"Jia","year":"2017","journal-title":"Nanoscale Res. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5519","DOI":"10.1007\/s11356-014-3717-7","article-title":"Cytotoxicity, DNA damage, and apoptosis induced by titanium dioxide nanoparticles in human non-small cell lung cancer A549 cells","volume":"22","author":"Wang","year":"2015","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Nazari, H., Heirani-Tabasi, A., Ghorbani, S., Eyni, H., Razavi Bazaz, S., Khayati, M., Gheidari, F., Moradpour, K., Kehtari, M., and Ahmadi Tafti, S.M. (2022). Microfluidic-Based Droplets for Advanced Regenerative Medicine: Current Challenges and Future Trends. Biosensors, 12.","DOI":"10.3390\/bios12010020"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8085","DOI":"10.2147\/IJN.S149070","article-title":"Zinc oxide nanoparticles induce toxic responses in human neuroblastoma SHSY5Y cells in a size-dependent manner","volume":"12","author":"Liu","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/jat.1385","article-title":"Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by four typical nanomaterials: The role of particle size, shape and composition","volume":"29","author":"Yang","year":"2009","journal-title":"J. Appl. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1080\/10934520600966177","article-title":"Toxicity of metal oxide nanoparticles in mammalian cells","volume":"41","author":"Jeng","year":"2006","journal-title":"J. Environ. Sci. Health A Tox. Hazard. Subst. Environ. Eng."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1289\/ehp.0901635","article-title":"Phosphorylation of p65 is required for zinc oxide nanoparticle-induced interleukin 8 expression in human bronchial epithelial cells","volume":"118","author":"Wu","year":"2010","journal-title":"Environ. Health Perspect."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1021\/tx1001892","article-title":"Titanium oxide shell coatings decrease the cytotoxicity of ZnO nanoparticles","volume":"24","author":"Hsiao","year":"2011","journal-title":"Chem. Res. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.colsurfb.2009.10.028","article-title":"Determination, characterization and cytotoxicity on HELF cells of ZnO nanoparticles","volume":"76","author":"Yuan","year":"2010","journal-title":"Colloids Surf. B. Biointerfaces"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S331","DOI":"10.1098\/rsif.2010.0068.focus","article-title":"Biomechanical effects of environmental and engineered particles on human airway smooth muscle cells","volume":"7","author":"Berntsen","year":"2010","journal-title":"J. R. Soc. Interface"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jare.2017.10.008","article-title":"A systematic review on silver nanoparticles-induced cytotoxicity: Physicochemical properties and perspectives","volume":"9","author":"Akter","year":"2018","journal-title":"J. Adv. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12295","DOI":"10.1038\/s41598-018-30541-3","article-title":"Gold nanoparticles-induced cytotoxicity in triple negative breast cancer involves different epigenetic alterations depending upon the surface charge","volume":"8","author":"Surapaneni","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_32","first-page":"100991","article-title":"Toxicity of gold nanoparticles (AuNPs): A review","volume":"26","author":"Sani","year":"2021","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"20","DOI":"10.7150\/thno.45413","article-title":"Silver nanoparticles: Synthesis, medical applications and biosafety","volume":"10","author":"Xu","year":"2020","journal-title":"Theranostics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4241","DOI":"10.2147\/IJN.S129748","article-title":"Stepwise pH-responsive nanoparticles for enhanced cellular uptake and on-demand intracellular release of doxorubicin","volume":"12","author":"Chen","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s12951-016-0217-6","article-title":"Zebrafish: A complete animal model to enumerate the nanoparticle toxicity","volume":"14","author":"Chakraborty","year":"2016","journal-title":"J. Nanobiotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e06577","DOI":"10.1016\/j.heliyon.2021.e06577","article-title":"Subchronic oral toxicity evaluation of gold nanoparticles in male and female mice","volume":"7","author":"Sun","year":"2021","journal-title":"Heliyon"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"927","DOI":"10.2217\/nnm-2020-0009","article-title":"Toxicity of alumina nanoparticles in the immune system of mice","volume":"15","author":"Li","year":"2020","journal-title":"Nanomedicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"253","DOI":"10.3389\/fphar.2018.00253","article-title":"Exposure to alumina nanoparticles in female mice during pregnancy induces neurodevelopmental toxicity in the offspring","volume":"9","author":"Zhang","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"94","DOI":"10.21608\/jcvr.2021.199440","article-title":"Potential Toxic Effects of Aluminum Nanoparticles: An overview","volume":"3","author":"Elkhadrawy","year":"2021","journal-title":"J. Curr. Vet. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"13841","DOI":"10.1021\/acsomega.2c00195","article-title":"Assessment of the Toxicity of Aluminum Oxide and Its Nanoparticles in the Bone Marrow and Liver of Male Mice: Ameliorative Efficacy of Curcumin Nanoparticles","volume":"7","author":"Alghriany","year":"2022","journal-title":"ACS Omega"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.etp.2005.05.008","article-title":"Metabolism and bioactivation of toxicants in the lung. The in vitro cellular approach","volume":"57","author":"Castell","year":"2005","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.tiv.2017.11.005","article-title":"Human lung epithelial cell cultures for analysis of inhaled toxicants: Lessons learned and future directions","volume":"47","author":"Hiemstra","year":"2018","journal-title":"Toxicol. Vitr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.etp.2005.05.011","article-title":"In vitro versus in vivo exposure to combustion emissions","volume":"57","author":"Seagrave","year":"2005","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1743-8977-6-32","article-title":"A dose-controlled system for air-liquid interface cell exposure and application to zinc oxide nanoparticles","volume":"6","author":"Lenz","year":"2009","journal-title":"Part. Fibre Toxicol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Diabat\u00e9, S., Armand, L., Murugadoss, S., Dilger, M., Fritsch-Decker, S., Schlager, C., B\u00e9al, D., Arnal, M.E., Biola-Clier, M., and Ambrose, S. (2020). Air-Liquid Interface Exposure of Lung Epithelial Cells to Low Doses of Nanoparticles to Assess Pulmonary Adverse Effects. Nanomaterials, 11.","DOI":"10.3390\/nano11010065"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1039\/c9tx00179d","article-title":"Nanoparticle induced barrier function assessment at liquid\u2013liquid and air\u2013liquid interface in novel human lung epithelia cell lines","volume":"8","author":"Leibrock","year":"2019","journal-title":"Toxicol. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"104714","DOI":"10.1016\/j.tiv.2019.104714","article-title":"In vitro inhalation cytotoxicity testing of therapeutic nanosystems for pulmonary infection","volume":"63","author":"Ritter","year":"2020","journal-title":"Toxicol. Vitr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1078\/0940-2993-00204","article-title":"In vitro exposure of isolated cells to native gaseous compounds\u2014Development and validation of an optimized system for human lung cells","volume":"53","author":"Ritter","year":"2001","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3389\/fbioe.2021.616830","article-title":"A Bioinspired in vitro Lung Model to Study Particokinetics of Nano-\/Microparticles Under Cyclic Stretch and Air-Liquid Interface Conditions","volume":"9","author":"Doryab","year":"2021","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Leibrock, L.B., Jungnickel, H., Tentschert, J., Katz, A., Toman, B., Petersen, E.J., Bierkandt, F.S., Singh, A.V., Laux, P., and Luch, A. (2020). Parametric optimization of an air-liquid interface system for flow through inhalation exposure to nanoparticles: Assessing dosimetry and intracellular uptake of CeO2 nanoparticles. Nanomaterials, 10.","DOI":"10.3390\/nano10122369"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1080\/01926230600713475","article-title":"The Nose Revisited: A Brief Review of the Comparative Structure, Function, and Toxicologic Pathology of the Nasal Epithelium","volume":"34","author":"Harkema","year":"2006","journal-title":"Toxicol. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/oxfordjournals.jncimonographs.a003443","article-title":"Biology of oral mucosa and esophagus","volume":"2001","author":"Squier","year":"2001","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/labinvest.2010.187","article-title":"Isolation of alveolar epithelial type II progenitor cells from adult human lungs","volume":"91","author":"Fujino","year":"2011","journal-title":"Lab. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"L493","DOI":"10.1152\/ajplung.1994.266.5.L493","article-title":"Calu-3: A human airway epithelial cell line that shows cAMP-dependent Cl- secretion","volume":"266","author":"Shen","year":"1994","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1046\/j.0022-3042.2001.00740.x","article-title":"Hydrocortisone decreases retinal endothelial cell water and solute flux coincident with increased content and decreased phosphorylation of occludin","volume":"80","author":"Antonetti","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.ejpb.2016.07.010","article-title":"Application of RPMI 2650 nasal cell model to a 3D printed apparatus for the testing of drug deposition and permeation of nasal products","volume":"107","author":"Pozzoli","year":"2016","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Ren, H., Birch, N.P., and Suresh, V. (2016). An optimised human cell culture model for alveolar epithelial transport. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0165225"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1177\/0960327112462725","article-title":"Nano-titanium dioxide induces genotoxicity and apoptosis in human lung cancer cell line, A549","volume":"32","author":"Srivastava","year":"2013","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.toxlet.2010.11.016","article-title":"In vitro toxicity evaluation of graphene oxide on A549 cells","volume":"200","author":"Chang","year":"2011","journal-title":"Toxicol. Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1089\/jam.2006.19.392","article-title":"An optimized in vitro model of the respiratory tract wall to study particle cell interactions","volume":"19","author":"Blank","year":"2006","journal-title":"J. Aerosol Med. Depos. Clear. Eff. Lung"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.omtm.2020.11.013","article-title":"A human surfactant B deficiency air-liquid interface cell culture model suitable for gene therapy applications","volume":"20","author":"Munis","year":"2021","journal-title":"Mol. Ther.\u2014Methods Clin. Dev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1080\/10611860290007504","article-title":"Permeability characteristics of Calu-3 human bronchial epithelial cells: In vitro-in vitro correlation to predict lung absorption in rats","volume":"10","author":"Mathias","year":"2002","journal-title":"J. Drug Target."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-5173(00)00452-X","article-title":"Characterization of the Calu-3 cell line as a tool to screen pulmonary drug delivery","volume":"208","author":"Foster","year":"2000","journal-title":"Int. J. Pharm."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s10544-013-9831-3","article-title":"A microdevice for parallelized pulmonary permeability studies","volume":"16","author":"Bol","year":"2014","journal-title":"Biomed. Microdevices"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1165\/rcmb.2006-0295OC","article-title":"8-iso-PGE2 stimulates anion efflux from airway epithelial cells via the EP4 prostanoid receptor","volume":"38","author":"Joy","year":"2008","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s12272-015-0704-6","article-title":"Functional and cytometric examination of different human lung epithelial cell types as drug transport barriers","volume":"39","author":"Min","year":"2016","journal-title":"Arch. Pharm. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1111\/j.2042-7158.2012.01540.x","article-title":"Cultivation of RPMI 2650 cells as an in-vitro model for human transmucosal nasal drug absorption studies: Optimization of selected culture conditions","volume":"64","author":"Reichl","year":"2012","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.ejpb.2009.08.008","article-title":"RPMI 2650 epithelial model and three-dimensional reconstructed human nasal mucosa as in vitro models for nasal permeation studies","volume":"74","author":"Wengst","year":"2010","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s11095-014-1494-0","article-title":"The characterization of the human nasal epithelial cell line RPMI 2650 under different culture conditions and their optimization for an appropriate in vitro nasal model","volume":"32","author":"Kreft","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1748459","DOI":"10.1080\/21688370.2020.1748459","article-title":"Optimization of an oral mucosa in vitro model based on cell line TR146","volume":"8","author":"Lin","year":"2020","journal-title":"Tissue Barriers"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1046\/j.0909-8836.1999.eos107210.x","article-title":"Filter-grown TR146 cells as an in vitro model of human buccal epithelial permeability","volume":"107","author":"Jacobsen","year":"1999","journal-title":"Eur. J. Oral Sci."},{"key":"ref_73","first-page":"e61210","article-title":"An air-liquid interface bronchial epithelial model for realistic, repeated inhalation exposure to airborne particles for toxicity testing","volume":"2020","author":"Braakhuis","year":"2020","journal-title":"J. Vis. Exp."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"105178","DOI":"10.1016\/j.tiv.2021.105178","article-title":"Inter-laboratory variability of A549 epithelial cells grown under submerged and air-liquid interface conditions","volume":"75","author":"Barosova","year":"2021","journal-title":"Toxicol. Vitr."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/s00204-010-0608-7","article-title":"Cytotoxicity of zinc oxide (ZnO) nanoparticles is influenced by cell density and culture format","volume":"85","author":"Heng","year":"2011","journal-title":"Arch. Toxicol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Leroux, M.M., Doumandji, Z., Ch\u00e9zeau, L., Gat\u00e9, L., Nahle, S., Hocquel, R., Zhernovkov, V., Migot, S., Ghanbaja, J., and Bonnet, C. (2020). Toxicity of TiO2 nanoparticles: Validation of alternative models. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21144855"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"8037","DOI":"10.2147\/IJN.S188175","article-title":"A comparative study of toxicity of TiO2, ZnO, and Ag nanoparticles to human aortic smooth-muscle cells","volume":"13","author":"Wang","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.msec.2015.03.053","article-title":"Morphological impact of zinc oxide particles on the antibacterial activity and human epithelia toxicity","volume":"52","author":"Hribar","year":"2015","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4542","DOI":"10.1039\/C5LC01028D","article-title":"Multi-layered, membrane-integrated microfluidics based on replica molding of a thiol-ene epoxy thermoset for organ-on-a-chip applications","volume":"15","author":"Sticker","year":"2015","journal-title":"Lab Chip"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"127946","DOI":"10.1016\/j.snb.2020.127946","article-title":"A lab-on-a-chip system with an embedded porous membrane-based impedance biosensor array for nanoparticle risk assessment on placental Bewo trophoblast cells","volume":"312","author":"Schuller","year":"2020","journal-title":"Sens. Actuators B Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.1021\/acs.analchem.7b04788","article-title":"Combinatorial in Vitro and in Silico Approach to Describe Shear-Force Dependent Uptake of Nanoparticles in Microfluidic Vascular Models","volume":"90","author":"Charwat","year":"2018","journal-title":"Anal. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"736","DOI":"10.3390\/bios5040736","article-title":"Microfluidic Impedimetric Cell Regeneration Assay to Monitor the Enhanced Cytotoxic Effect of Nanomaterial Perfusion","volume":"5","author":"Rothbauer","year":"2015","journal-title":"Biosensors"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5634\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:55:55Z","timestamp":1760122555000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,15]]},"references-count":82,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24065634"],"URL":"https:\/\/doi.org\/10.3390\/ijms24065634","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,15]]}}}