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Age-Dependent Rat Lung Deposition Patterns of Inhaled 20 Nanometer Gold Nanoparticles and their Quantitative Biokinetics in Adult Rats

Kreyling, Wolfgang G., Möller, Winfried, Holzwarth, Uwe, Hirn, Stephanie, Wenk, Alexander, Schleh, Carsten, Schäffler, Martin, Haberl, Nadine, Gibson, Neil, Schittny, Johannes C.·2018·ACS Nano
DOI 10.1021/acsnano.8b01826
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Abstract

The increasing use of gold nanoparticles leads to a possible increase of exposure by inhalation. Therefore, we have studied the deposition patterns of inhaled 20 nm gold nanoparticles (AuNP) in 7−90 day old rats and their biokinetics in 60 day old ones. Wistar−Kyoto rats inhaled intratracheally 20 nm 195Au-radiolabeled AuNP by negative pressure ventilation over 2 h. Immediately afterward lungs were excised, inflated and microwave dried. AuNP deposition was analyzed by single-photon emission computed tomography, computed-tomography and autoradiography. Completely balanced, quantitative biodistributions in major organs and all body tissues and total excretion were analyzed from 1 h to 28 d after inhalation. Intratracheal inhalation caused AuNP deposition predominately in the caudal lungs, independent of age. About 30% AuNP were deposited on airway epithelia and rapidly cleared by mucociliary clearance. About 80% of AuNP deposited in alveoli was relocated from the epithelium into the interstitium within 24 h and was inaccessible to broncho-alveolar lavage. During interstitial long-term retention, re-entrainment within macrophages back onto the lung epithelium and to the larynx and gastrointestinal tract (GIT) dominated AuNP clearance (rate 0.03 d−1) In contrast, AuNP-translocation across the air−blood barrier was much smaller leading to persistent retention in secondary organs and tissues in the ranking order liver > soft issue > spleen > kidneys > skeleton > blood > uterus > heart > brain. The age-independent, inhomogeneous AuNP deposition was probably caused by the negative pressure ventilation. Long-term AuNP clearance was dominated by macrophage-mediated transport from the interstitium to the larynx and GIT. Translocation across the rat air−blood barrier appeared to be similar to that of humans for similar sized AuNP.

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Research works printed but not linked: 79

  1. Ciriminna, 2016, Industrial Applications of Gold Catalysis, Angew. Chem., Int. Ed., 55, 14210, 10.1002/anie.201604656 · DOI
  2. Villa, 2015, Glycerol Oxidation Using Gold-Containing Catalysts, Acc. Chem. Res., 48, 1403, 10.1021/ar500426g · DOI
  3. Heo, 2014, Synthesis of Mono-Dispersed Nanofluids Using Solution Plasma, J. Appl. Phys., 116, 024302, 10.1063/1.4887806 · DOI
  4. Morgan, 2014, Application of Halohydrocarbons for the Re-Dispersion of Gold Particles, Catal. Sci. Technol., 4, 729, 10.1039/c3cy00915g · DOI
  5. Johnston, 2010, A Review of the in Vivo and in Vitro Toxicity of Silver and Gold Particulates: Particle Attributes and Biological Mechanisms Responsible for the Observed Toxicity, Crit. Rev. Toxicol., 40, 328, 10.3109/10408440903453074 · DOI
  6. Khlebtsov, 2011, Biodistribution and Toxicity of Engineered Gold Nanoparticles: A Review of in Vitro and in Vivo Studies, Chem. Soc. Rev., 40, 1647, 10.1039/C0CS00018C · DOI
  7. Kermanizadeh, 2015, Nanomaterial Translocation–the Biokinetics, Tissue Accumulation, Toxicity and Fate of Materials in Secondary Organs–a Review, Crit. Rev. Toxicol., 45, 837, 10.3109/10408444.2015.1058747 · DOI
  8. Hamzawy, 2017, Antitumor Activity of Intratracheal Inhalation of Temozolomide (Tmz) Loaded into Gold Nanoparticles and/or Liposomes against Urethane-Induced Lung Cancer in Balb/C Mice, Drug Delivery, 24, 599, 10.1080/10717544.2016.1247924 · DOI
  9. Hao, 2015, Potential for Enhancing External Beam Radiotherapy for Lung Cancer Using High-Z Nanoparticles Administered Via Inhalation, Phys. Med. Biol., 60, 7035, 10.1088/0031-9155/60/18/7035 · DOI
  10. Balasubramanian, 2013, The Effect of Primary Particle Size on Biodistribution of Inhaled Gold Nano-Agglomerates, Biomaterials, 34, 5439, 10.1016/j.biomaterials.2013.03.080 · DOI
  11. Han, 2015, Size-Dependent Clearance of Gold Nanoparticles from Lungs of Sprague-Dawley Rats after Short-Term Inhalation Exposure, Arch. Toxicol., 89, 1083, 10.1007/s00204-014-1292-9 · DOI
  12. Oberdörster, 2018, In Vivo Effects: Methodologies and Biokinetics of Inhaled Nanomaterials, NanoImpact, 10, 38, 10.1016/j.impact.2017.10.007 · DOI · Paper page
  13. Miller, 2017, Inhaled Nanoparticles Accumulate at Sites of Vascular Disease, ACS Nano, 11, 4542, 10.1021/acsnano.6b08551 · DOI
  14. Semmler-Behnke, 2007, Efficient Elimination of Inhaled Nanoparticles from the Alveolar Region: Evidence for Interstitial Uptake and Subsequent Reentrainment onto Airways Epithelium, Environ. Health Perspect., 115, 728, 10.1289/ehp.9685 · DOI · Paper page
  15. Semmler, 2004, Long-Term Clearance Kinetics of Inhaled Ultrafine Insoluble Iridium Particles from the Rat Lung, Including Transient Translocation into Secondary Organs, Inhalation Toxicol., 16, 453, 10.1080/08958370490439650 · DOI · Paper page
  16. Kreyling, 2002, Translocation of Ultrafine Insoluble Iridium Particles from Lung Epithelium to Extrapulmonary Organs Is Size Dependent but Very Low, J. Toxicol. Environ. Health, Part A, 65, 1513, 10.1080/00984100290071649 · DOI · Paper page
  17. Ellender, 1992, Effect of Bronchopulmonary Lavage on Lung Retention and Clearance of Particulate Material in Hamsters, Environ. Health Perspect., 97, 209, 10.1289/ehp.9297209 · DOI · Paper page
  18. Lehnert, 1989, Alveolar Macrophage-Particle Relationships During Lung Clearance, Am. J. Respir. Cell Mol. Biol., 1, 145, 10.1165/ajrcmb/1.2.145 · DOI · Paper page
  19. Semmler-Behnke, 2012, Nanoparticle Delivery in Infant Lungs, Proc. Natl. Acad. Sci. U. S. A., 109, 5092, 10.1073/pnas.1119339109 · DOI
  20. Kreyling, 2014, Air-Blood Barrier Translocation of Tracheally Instilled Gold Nanoparticles Inversely Depends on Particle Size, ACS Nano, 8, 222, 10.1021/nn403256v · DOI · Paper page
  21. Schleh, 2012, Size and Surface Charge of Gold Nanoparticles Determine Absorption across Intestinal Barriers and Accumulation in Secondary Target Organs after Oral Administration, Nanotoxicology, 6, 36, 10.3109/17435390.2011.552811 · DOI · Paper page
  22. Hirn, 2011, Particle Size-Dependent and Surface Charge-Dependent Biodistribution of Gold Nanoparticles after Intravenous Administration, Eur. J. Pharm. Biopharm., 77, 407, 10.1016/j.ejpb.2010.12.029 · DOI
  23. Hume, 2008, Differentiation and Heterogeneity in the Mononuclear Phagocyte System, Mucosal Immunol., 1, 432, 10.1038/mi.2008.36 · DOI
  24. Almeida, 2011, In Vivo Biodistribution of Nanoparticles, Nanomedicine (London, U. K.), 6, 815, 10.2217/nnm.11.79 · DOI
  25. Zarschler, 2016, Ultrasmall Inorganic Nanoparticles: State-of-the-Art and Perspectives for Biomedical Applications, Nanomedicine (N. Y., NY, U. S.), 12, 1663, 10.1016/j.nano.2016.02.019 · DOI
  26. Kreyling, 2017, Quantitative Biokinetics of Titanium Dioxide Nanoparticles after Intravenous Injection in Rats: Part 1, Nanotoxicology, 11, 434, 10.1080/17435390.2017.1306892 · DOI
  27. Kreyling, 2017, Quantitative Biokinetics of Titanium Dioxide Nanoparticles after Intratracheal Instillation in Rats: Part 3, Nanotoxicology, 11, 454, 10.1080/17435390.2017.1306894 · DOI
  28. Takenaka, 2006, Distribution Pattern of Inhaled Ultrafine Gold Particles in the Rat Lung, Inhalation Toxicol., 18, 733, 10.1080/08958370600748281 · DOI
  29. Takenaka, 2012, Efficient Internalization and Intracellular Translocation of Inhaled Gold Nanoparticles in Rat Alveolar Macrophages, Nanomedicine (London, U. K.), 7, 855, 10.2217/nnm.11.152 · DOI
  30. Schleh, 2013, Biodistribution of Inhaled Gold Nanoparticles in Mice and the Influence of Surfactant Protein D, J. Aerosol Med. Pulm. Drug Delivery, 26, 24, 10.1089/jamp.2011.0951 · DOI
  31. Tschanz, 2014, Rat Lungs Show a Biphasic Formation of New Alveoli During Postnatal Development, J. Appl. Physiol., 117, 89, 10.1152/japplphysiol.01355.2013 · DOI
  32. Barré, 2016, The Total Number of Acini Remains Constant Throughout Postnatal Rat Lung Development, Am.J. Physiol.-Lung Cell. Mol. Physiol., 311, L1082, 10.1152/ajplung.00325.2016 · DOI
  33. Hofemeier, 2018, One (Sub-)Acinus for All: Fate of Inhaled Aerosols in Heterogeneous Pulmonary Acinar Structures, Eur. J. Pharm. Sci., 113, 53, 10.1016/j.ejps.2017.09.033 · DOI
  34. Schittny, 2017, Computational Model of a Breathing Lung Illustrates the Influence of the Acinar Structures on Gas Washout, Am. J. Respir. Crit. Care Med., 195, A4440
  35. Tschanz, 2014, Rat Lungs Show a Biphasic Formation of New Alveoli During Postnatal Development, J. Appl. Physiol., 117, 89, 10.1152/japplphysiol.01355.2013 · DOI
  36. Hughes, 1985, Regional Ventilation Distribution, 177
  37. Brown, 2015, Deposition of Particles, 513, 10.1016/B978-0-12-404577-4.00027-8 · DOI
  38. 1994, Human Respiratory Tract Model for Radiological Protection. A Report of a Task Group of the International Commission on Radiological Protection, Ann. ICRP, 24, 1
  39. Oberdorster, 1992, Volumetric Loading of Alveolar Macrophages (Am): A Possible Basis for Diminished Am-Mediated Particle Clearance, Exp. Lung Res., 18, 87, 10.3109/01902149209020653 · DOI
  40. Kreyling, 2000, Clearance of Particles Deposited in the Lungs, 323
  41. Kreyling, 1990, Interspecies Comparison of Lung Clearance of ″Insoluble, J. Aerosol Med., 3, S93, 10.1089/jam.1990.3.Suppl_1.S-93 · DOI
  42. Lehnert, 1992, Pulmonary and Thoracic Macrophage Subpopulations and Clearance of Particles from the Lung, Environ. Health Perspect., 97, 17, 10.1289/ehp.929717 · DOI · Paper page
  43. Adamson, 1978, Adaptive Responses of the Pulmonary Macrophagic System to Carbon. II. Morphologic Studies, Lab. Invest., 38, 430
  44. Adamson, 1981, Dose Response of the Pulmonary Macrophagic System to Various Particulates and Its Relationship to Transepithelial Passage of Free Particles, Exp. Lung Res., 2, 165, 10.3109/01902148109052312 · DOI · Paper page
  45. Bowden, 1984, Pathways of Cellular Efflux and Particulate Clearance after Carbon Instillation to the Lung, J. Pathol., 143, 117, 10.1002/path.1711430206 · DOI · Paper page
  46. Thorley, 2014, Critical Determinants of Uptake and Translocation of Nanoparticles by the Human Pulmonary Alveolar Epithelium, ACS Nano, 8, 11778, 10.1021/nn505399e · DOI · Paper page
  47. Geiser, 2005, Ultrafine Particles Cross Cellular Membranes by Nonphagocytic Mechanisms in Lungs and in Cultured Cells. Environ, Health Perspect, 113, 1555, 10.1289/ehp.8006 · DOI
  48. Nunn, 1993, Functional Anatomy of the Respiratory Tract, 13, 10.1016/B978-0-7506-1336-1.50008-5 · DOI
  49. Weibel, 2015, On the Tricks Alveolar Epithelial Cells Play to Make a Good Lung, Am. J. Respir. Crit. Care Med., 191, 504, 10.1164/rccm.201409-1663OE · DOI
  50. Macklin, 2004, Pulmonary Sumps, Dust Accumulations, Alveolar Fluid and Lymph Vessels, Cells Tissues Organs, 23, 1, 10.1159/000140979 · DOI
  51. Oberdörster, 2005, Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles, Environ. Health Perspect, 113, 823, 10.1289/ehp.7339 · DOI · Paper page
  52. Plesch, 1982, Histology and Immunohistochemistry of Bronchus Associated Lymphoid Tissue (Balt) in the Rat, Adv. Exp. Med. Biol., 149, 491, 10.1007/978-1-4684-9066-4_69 · DOI
  53. Fromen, 2016, Nanoparticle Surface Charge Impacts Distribution, Uptake and Lymph Node Trafficking by Pulmonary Antigen-Presenting Cells, Nanomedicine (N. Y., NY, U. S.), 12, 677, 10.1016/j.nano.2015.11.002 · DOI
  54. Roth, 1993, Proceedings of the 1993 European Aerosol Conference 14 O 04 Clearance of the Human Lungs for Ultrafine Particles, J. Aerosol Sci., 24, S95, 10.1016/0021-8502(93)90140-5 · DOI
  55. Wagner, 2004, Health Effects of Ultrafine Particles, J. Aerosol Sci., 35, 1155, 10.1016/j.jaerosci.2004.06.029 · DOI
  56. Möller, 2001, Human Alveolar Long-Term Clearance of Ferromagnetic Iron Oxide Microparticles in Healthy and Diseased Subjects, Exp. Lung Res., 27, 547, 10.1080/019021401753181827 · DOI
  57. Möller, 2008, Deposition, Retention, and Translocation of Ultrafine Particles from the Central Airways and Lung Periphery, Am. J. Respir. Crit. Care Med., 177, 426, 10.1164/rccm.200602-301OC · DOI
  58. Snipes, 1983, Retention of Monodisperse or Polydisperse Aluminosilicate Particles Inhaled by Dogs, Rats, and Mice, Toxicol. Appl. Pharmacol., 69, 345, 10.1016/0041-008X(83)90258-2 · DOI
  59. Pan, 2009, Gold Nanoparticles of Diameter 1.4 Nm Trigger Necrosis by Oxidative Stress and Mitochondrial Damage, Small, 5, 2067, 10.1002/smll.200900466 · DOI
  60. Pan, 2007, Size-Dependent Cytotoxicity of Gold Nanoparticles, Small, 3, 1941, 10.1002/smll.200700378 · DOI
  61. Tsoli, 2005, Cellular Uptake and Toxicity of Au55 Clusters, Small, 1, 841, 10.1002/smll.200500104 · DOI
  62. Kreyling, 2017, Quantitative Biokinetics of Titanium Dioxide Nanoparticles after Oral Application in Rats: Part 2, Nanotoxicology, 11, 443, 10.1080/17435390.2017.1306893 · DOI
  63. Hainfeld, 2006, Gold Nanoparticles: A New X-Ray Contrast Agent, Br. J. Radiol., 79, 248, 10.1259/bjr/13169882 · DOI
  64. Hainfeld, 2004, The Use of Gold Nanoparticles to Enhance Radiotherapy in Mice, Phys. Med. Biol., 49, N309, 10.1088/0031-9155/49/18/N03 · DOI
  65. Choi, 2007, Renal Clearance of Quantum Dots, Nat. Biotechnol., 25, 1165, 10.1038/nbt1340 · DOI · Paper page
  66. Alric, 2013, The Biodistribution of Gold Nanoparticles Designed for Renal Clearance, Nanoscale, 5, 5930, 10.1039/c3nr00012e · DOI
  67. Chen, 2016, Dynamic Positron Emission Tomography Imaging of Renal Clearable Gold Nanoparticles, Small, 12, 2775, 10.1002/smll.201600194 · DOI
  68. Miller, 2017, Correction to″Inhaled Nanoparticles Accumulate at Sites of Vascular Disease″, ACS Nano, 11, 10623, 10.1021/acsnano.7b06327 · DOI
  69. Möller, 2013, Gold Nanoparticle Aerosols for Rodent Inhalation and Translocation Studies, J. Nanopart. Res., 15, 1574, 10.1007/s11051-013-1574-9 · DOI
  70. Ditroi, 2016, Activation Cross Sections of Proton Induced Nuclear Reactions on Gold up to 65 Mev, Appl. Radiat. Isot., 113, 96, 10.1016/j.apradiso.2016.04.020 · DOI
  71. Alessandrini, 2008, Total and Regional Deposition of Ultrafine Particles in a Mouse Model of Allergic Inflammation of the Lung, Inhalation Toxicol., 20, 585, 10.1080/08958370801949167 · DOI
  72. Kreyling, 2009, Size Dependence of the Translocation of Inhaled Iridium and Carbon Nanoparticle Aggregates from the Lung of Rats to the Blood and Secondary Target Organs, Inhalation Toxicol., 21, 55, 10.1080/08958370902942517 · DOI
  73. Kreyling, 2016, Discovery of Unique and Enm─ Specific Pathophysiologic Pathways: Comparison of the Translocation of Inhaled Iridium Nanoparticles from Nasal Epithelium Versus Alveolar Epithelium Towards the Brain of Rats, Toxicol. Appl. Pharmacol., 299, 41, 10.1016/j.taap.2016.02.004 · DOI
  74. Haberthür, 2009, Multimodal Imaging for the Detection of Sub-Micron Particles in the Gas-Exchange Region of the Mammalian Lung, J. Phys.: Conf. Ser., 186, 012040, 10.1088/1742-6596/186/1/012040 · DOI
  75. Sweeney, 1987, Emphysema Alters the Deposition Pattern of Inhaled Particles in Hamsters, Am. J. Physiol., 128, 19
  76. Valberg, 1982, Breathing Patterns Influence Aerosol Deposition Sites in Excised Dog Lungs, J. Appl. Physiol., 53, 824, 10.1152/jappl.1982.53.4.824 · DOI
  77. Schindelin, 2012, Fiji: An Open-Source Platform for Biological-Image Analysis., Nat. Methods, 9, 676, 10.1038/nmeth.2019 · DOI · Paper page
  78. Oeff, 1955, [Blood Volume of Rat Organs and Residual Amount of Blood after Blood Letting or Irrigation; Determination with Radiophosphorus-Labeled Erythrocytes.], Naunyn-Schmiedeberg's Arch. Pharmacol., 226, 98, 10.1007/BF00246232 · DOI
  79. Kreyling, 2014, Air–Blood Barrier Translocation of Tracheally Instilled Gold Nanoparticles Inversely Depends on Particle Size, ACS Nano, 8, 222, 10.1021/nn403256v · DOI · Paper page

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Authors
Kreyling, W. G., Möller, W., Holzwarth, U., Hirn, S., Wenk, A., Schleh, C., Schäffler, M., Haberl, N., Gibson, N., & Schittny, J. C.
Venue
ACS Nano
Publisher
American Chemical Society (ACS)
Published
2018-08-07
Volume
12
Issue
8
Pages
7771-7790
ISSN
  • 1936-0851
  • 1936-086X
DOI
10.1021/acsnano.8b01826
Cited by
87
References
1
Language
en
Licence
pubs.acs.org/page/policy/authorchoice_termsofuse.html (vor, 10 d)
Funders
  • European Commission (214547, 228625, 228789, 012912)
  • Schweizerischer Nationalfonds zur F?rderung der Wissenschaftlichen Forschung (310030_153468, 310030_175953)
  • U.S. Department of Health and Human Services (HL074022)
  • Deutsche Forschungsgemeinschaft (SPP 1313)

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CoChat. (2026). Citation check: Age-Dependent Rat Lung Deposition Patterns of Inhaled 20 Nanometer Gold Nanoparticles and their Quantitative Biokinetics in Adult Rats. https://app.cochat.ai/papers/10.1021/acsnano.8b01826
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Kreyling, W. G., Möller, W., Holzwarth, U., Hirn, S., Wenk, A., Schleh, C., Schäffler, M., Haberl, N., Gibson, N., & Schittny, J. C. (2018). Age-Dependent Rat Lung Deposition Patterns of Inhaled 20 Nanometer Gold Nanoparticles and their Quantitative Biokinetics in Adult Rats. ACS Nano. https://doi.org/10.1021/acsnano.8b01826