{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:41:58Z","timestamp":1788259318711,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,30]],"date-time":"2022-01-30T00:00:00Z","timestamp":1643500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2021R1I1A3054949"],"award-info":[{"award-number":["NRF-2021R1I1A3054949"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002632","name":"Hallym University","doi-asserted-by":"publisher","award":["Hallym University Research Fund"],"award-info":[{"award-number":["Hallym University Research Fund"]}],"id":[{"id":"10.13039\/501100002632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Understanding the interaction between nanoparticles and immune cells is essential for the evaluation of nanotoxicity and development of nanomedicines. However, to date, there is little data on the membrane microstructure and biochemical changes in nanoparticle-loaded immune cells. In this study, we observed the microstructure of nanoparticle-loaded macrophages and changes in lipid droplets using holotomography analysis. Quantitatively analyzing the refractive index distribution of nanoparticle-loaded macrophages, we identified the interactions between nanoparticles and macrophages. The results showed that, when nanoparticles were phagocytized by macrophages, the number of lipid droplets and cell volume increased. The volume and mass of the lipid droplets slightly increased, owing to the absorption of nanoparticles. Meanwhile, the number of lipid droplets increased more conspicuously than the other factors. Furthermore, alveolar macrophages are involved in the development and progression of asthma. Studies have shown that macrophages play an essential role in the maintenance of asthma-related inflammation and tissue damage, suggesting that macrophage cells may be applied to asthma target delivery strategies. Therefore, we investigated the target delivery efficiency of gold nanoparticle-loaded macrophages at the biodistribution level, using an ovalbumin-induced asthma mouse model. Normal and severe asthma models were selected to determine the difference in the level of inflammation in the lung. Consequently, macrophages had increased mobility in models of severe asthma, compared to those of normal asthma disease. In this regard, the detection of observable differences in nanoparticle-loaded macrophages may be of primary interest, as an essential endpoint analysis for investigating nanomedical applications and immunotheragnostic strategies.<\/jats:p>","DOI":"10.3390\/ijms23031622","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T01:46:08Z","timestamp":1643593568000},"page":"1622","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Interactions of Nanoparticles with Macrophages and Feasibility of Drug Delivery for Asthma"],"prefix":"10.3390","volume":"23","author":[{"given":"Sung Hun","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Hallym University College of Medicine, Chuncheon 24252, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoo Seob","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8156-1886","authenticated-orcid":false,"given":"Dong-Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Il Seok","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Hallym University College of Medicine, Dongtan Sacred Heart Hospital, 7, Keunjaebong-gil, Hwaseong-si 18450, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6317-9525","authenticated-orcid":false,"given":"Sung Kyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Hallym University College of Medicine, Dongtan Sacred Heart Hospital, 7, Keunjaebong-gil, Hwaseong-si 18450, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DongHun","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Physics, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YongKeun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Physics, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea"},{"name":"Tomocube, Inc., Daejeon 34051, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0739-7971","authenticated-orcid":false,"given":"Soo-Hwan","family":"Byun","sequence":"additional","affiliation":[{"name":"Department of Oral & Maxillofacial Surgery, Dentistry, Hallym University College of Medicine, Hallym Sacred Heart Hospital, Anyang 14068, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0599-875X","authenticated-orcid":false,"given":"Jeong-Hee","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pulmonology and Allergy, Hallym University College of Medicine, Dongtan Sacred Heart Hospital, 7, Keunjaebong-gil, Hwaseong-si 18450, Korea"},{"name":"Allergy and Clinical Immunology Research Center, Hallym University College of Medicine, Chuncheon 24252, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9061-0552","authenticated-orcid":false,"given":"Seok Jin","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Hallym University College of Medicine, Dongtan Sacred Heart Hospital, 7, Keunjaebong-gil, Hwaseong-si 18450, Korea"},{"name":"Allergy and Clinical Immunology Research Center, Hallym University College of Medicine, Chuncheon 24252, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1700818","DOI":"10.1002\/adhm.201700818","article-title":"Cell-Based Drug Delivery and Use of Nano-and Microcarriers for Cell Functionalization","volume":"7","author":"Timin","year":"2018","journal-title":"Adv. Healthc. Mater."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ejps.2016.07.021","article-title":"Advances of blood cell-based drug delivery systems","volume":"96","author":"Sun","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Swartzwelter, B.J., Verde, A., Rehak, L., Madej, M., Puntes, V.F., De Luca, A.C., Boraschi, D., and Italiani, P. (2021). Interaction between Macrophages and Nanoparticles: In Vitro 3D Cultures for the Realistic Assessment of Inflammatory Activation and Modulation of Innate Memory. Nanomaterials, 11.","DOI":"10.3390\/nano11010207"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.tcb.2020.09.006","article-title":"Lipid Metabolism in Regulation of Macrophage Functions","volume":"30","author":"Yan","year":"2020","journal-title":"Trends Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.3389\/fmicb.2018.01951","article-title":"Methods for Lipid Droplet Biophysical Characterization in Flaviviridae Infections","volume":"9","author":"Martins","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41566-018-0253-x","article-title":"Quantitative phase imaging in biomedicine","volume":"12","author":"Park","year":"2018","journal-title":"Nat. Photonics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6524","DOI":"10.1038\/s41598-018-24393-0","article-title":"Label-free non-invasive quantitative measurement of lipid contents in individual microalgal cells using refractive index tomography","volume":"8","author":"Jung","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1021\/acsnano.9b07993","article-title":"Label-Free Tomographic Imaging of Lipid Droplets in Foam Cells for Machine-Learning-Assisted Therapeutic Evaluation of Targeted Nanodrugs","volume":"14","author":"Park","year":"2020","journal-title":"ACS Nano"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7168","DOI":"10.1021\/acs.nanolett.0c02463","article-title":"Surface charge-dependent cytotoxicity of plastic nanoparticles in alveolar cells under cyclic stretches","volume":"20","author":"Roshanzadeh","year":"2020","journal-title":"Nano Lett."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yhee, J.Y., Im, J., and Nho, R.S. (2016). Advanced Therapeutic Strategies for Chronic Lung Disease Using Nanoparticle-Based Drug Delivery. J. Clin. Med., 5.","DOI":"10.3390\/jcm5090082"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.cbi.2019.02.021","article-title":"Interactions with the macrophages: An emerging targeted approach using novel drug delivery systems in respiratory diseases","volume":"304","author":"Mehta","year":"2019","journal-title":"Chem. Biol. Interact."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/nrd4363","article-title":"Overcoming the challenges in administering biopharmaceuticals: Formulation and delivery strategies","volume":"13","author":"Mitragotri","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.micron.2014.03.012","article-title":"Detection of lipopolysaccharide induced inflammatory responses in RAW264.7 macrophages using atomic force microscope","volume":"65","author":"Pi","year":"2014","journal-title":"Micron"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.apsb.2015.01.010","article-title":"Neocryptotanshinone inhibits lipopolysaccharide-induced inflammation in RAW264.7 macrophages by suppression of NF-\u03baB and iNOS signaling pathways","volume":"5","author":"Wu","year":"2015","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1016\/j.fct.2010.05.020","article-title":"Rheosmin, a naturally occurring phenolic compound inhibits LPS-induced iNOS and COX-2 expression in RAW264.7 cells by blocking NF-\u03baB activation pathway","volume":"48","author":"Jeong","year":"2010","journal-title":"Food Chem. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.plefa.2010.02.005","article-title":"Lipid droplets in inflammation and cancer","volume":"82","author":"Bozza","year":"2010","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids (PLEFA)"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s00418-002-0462-7","article-title":"Deformation of lipid droplets in fixed samples","volume":"118","author":"Fukumoto","year":"2002","journal-title":"Histochem. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Bianchi, J.I., Stockert, J.C., Buzz, L.I., Bl\u00e1zquez-Castro, A., and Simonetta, S.H. (2015). Reliable Screening of Dye Phototoxicity by Using a Caenorhabditis elegans Fast Bioassay. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128898"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.apsb.2017.12.001","article-title":"Leukocyte-derived biomimetic nanoparticulate drug delivery systems for cancer therapy","volume":"8","author":"Huang","year":"2018","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kim, S., Kang, S.H., Byun, S.H., Kim, H.-J., Park, I.-K., Hirschberg, H., and Hong, S.J. (2020). Intercellular Bioimaging and Biodistribution of Gold Nanoparticle-Loaded Macrophages for Targeted Drug Delivery. Electronics, 9.","DOI":"10.3390\/electronics9071105"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5869235","DOI":"10.1155\/2020\/5869235","article-title":"Biomimetic Gold Nanoshell-Loaded Macrophage for Photothermal Biomedicine","volume":"2020","author":"Kang","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1146\/annurev-pathol-011811-132445","article-title":"The Cell Biology of Phagocytosis","volume":"7","author":"Flannagan","year":"2012","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.immuni.2016.02.026","article-title":"Phagocytosis: An Immunobiologic Process","volume":"44","author":"Gordon","year":"2016","journal-title":"Immunity"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1021\/mp900098p","article-title":"Lipid Droplets: Their Role in Nanoparticle-Induced Oxidative Stress","volume":"6","author":"Khatchadourian","year":"2009","journal-title":"Mol. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/j.chembiol.2005.09.008","article-title":"Unmodified Cadmium Telluride Quantum Dots Induce Reactive Oxygen Species Formation Leading to Multiple Organelle Damage and Cell Death","volume":"12","author":"Cho","year":"2005","journal-title":"Chem. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.tiv.2006.01.021","article-title":"Consequences of mitochondrial injury induced by pharmaceutical fatty acid oxidation inhibitors is characterized in human and rat liver slices","volume":"20","author":"Vickers","year":"2006","journal-title":"Toxicol. In Vitro"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1007\/s00011-006-5205-0","article-title":"Lipid bodies: Structural markers of inflammatory macrophages in innate immunity","volume":"55","author":"Melo","year":"2006","journal-title":"Inflamm. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.pharmthera.2018.01.004","article-title":"Towards targeting resolution pathways of airway inflammation in asthma","volume":"186","author":"Barnig","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1146\/annurev-physiol-021113-170408","article-title":"Resolution of Acute Inflammation in the Lung","volume":"76","author":"Levy","year":"2014","journal-title":"Annu. Rev. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nri2294","article-title":"Resolving inflammation: Dual anti-inflammatory and pro-resolution lipid mediators","volume":"8","author":"Serhan","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e243","DOI":"10.1038\/emm.2016.38","article-title":"The role of autophagy in allergic inflammation: A new target for severe asthma","volume":"48","author":"Liu","year":"2016","journal-title":"Exp. Mol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e113","DOI":"10.1038\/emm.2014.55","article-title":"Attenuation of airway inflammation by simvastatin and the implications for asthma treatment: Is the jury still out?","volume":"46","author":"Liu","year":"2014","journal-title":"Exp. Mol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.pdpdt.2017.12.002","article-title":"Photochemical internalization enhanced macrophage delivered chemotherapy","volume":"21","author":"Shin","year":"2018","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"15700","DOI":"10.1021\/jp061667w","article-title":"Turkevich Method for Gold Nanoparticle Synthesis Revisited","volume":"110","author":"Kimling","year":"2006","journal-title":"J. Phys. Chem. B"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jiec.2017.08.019","article-title":"Preparation of blue-color-emitting graphene quantum dots and their in vitro and in vivo toxicity evaluation","volume":"57","author":"Nafiujjaman","year":"2018","journal-title":"J. Ind. Eng. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5407","DOI":"10.1364\/OL.40.005407","article-title":"Active illumination using a digital micromirror device for quantitative phase imaging","volume":"40","author":"Shin","year":"2015","journal-title":"Opt. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0030-4018(69)90052-2","article-title":"Three-dimensional structure determination of semi-transparent objects from holographic data","volume":"1","author":"Wolf","year":"1969","journal-title":"Opt. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Shin, S., Kim, K., Kim, T., Yoon, J., Hong, K., Park, J., and Park, Y. (2016). Optical Diffraction Tomography Using a Digital Micromirror Device for Stable Measurements of 4D Refractive Index Tomography of Cells, International Society for Optics and Photonics.","DOI":"10.1117\/12.2216769"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"011005","DOI":"10.1117\/1.JBO.19.1.011005","article-title":"High-resolution three-dimensional imaging of red blood cells parasitized by Plasmodium falciparum and in situ hemozoin crystals using optical diffraction tomography","volume":"19","author":"Kim","year":"2013","journal-title":"J. Biomed. Opt."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1038\/1721097a0","article-title":"Determination of dry mass, thickness, solid and water concentration in living cells","volume":"172","author":"Barer","year":"1953","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"C538","DOI":"10.1152\/ajpcell.00121.2008","article-title":"Optical imaging of cell mass and growth dynamics","volume":"295","author":"Popescu","year":"2008","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1016\/j.bpj.2011.03.004","article-title":"On the distribution of protein refractive index increments","volume":"100","author":"Zhao","year":"2011","journal-title":"Biophys. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.1021\/ac800027s","article-title":"Optical Anisotropy of Supported Lipid Structures Probed by Waveguide Spectroscopy and Its Application to Study of Supported Lipid Bilayer Formation Kinetics","volume":"80","author":"Mashaghi","year":"2008","journal-title":"Anal. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"36815","DOI":"10.1038\/srep36815","article-title":"Three-dimensional label-free imaging and quantification of lipid droplets in live hepatocytes","volume":"6","author":"Kim","year":"2016","journal-title":"Sci. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1622\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:11:39Z","timestamp":1760134299000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1622"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,30]]},"references-count":44,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijms23031622"],"URL":"https:\/\/doi.org\/10.3390\/ijms23031622","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,30]]}}}