{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:21:50Z","timestamp":1785424910913,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"crossref","award":["TSGH_D_114053"],"award-info":[{"award-number":["TSGH_D_114053"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"crossref","award":["TSGH_D_114147"],"award-info":[{"award-number":["TSGH_D_114147"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"crossref","award":["TSGH_E_114261"],"award-info":[{"award-number":["TSGH_E_114261"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"crossref","award":["TSGH_D_114122"],"award-info":[{"award-number":["TSGH_D_114122"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"crossref","award":["TSGH_E_115259"],"award-info":[{"award-number":["TSGH_E_115259"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"crossref"}]},{"award":["TSGH_D_114053"],"award-info":[{"award-number":["TSGH_D_114053"]}],"id":[{"id":"https:\/\/ror.org\/007h4qe29","id-type":"ROR","asserted-by":"publisher"}]},{"award":["TSGH_D_114147"],"award-info":[{"award-number":["TSGH_D_114147"]}],"id":[{"id":"https:\/\/ror.org\/007h4qe29","id-type":"ROR","asserted-by":"publisher"}]},{"award":["TSGH_E_114261"],"award-info":[{"award-number":["TSGH_E_114261"]}],"id":[{"id":"https:\/\/ror.org\/007h4qe29","id-type":"ROR","asserted-by":"publisher"}]},{"award":["TSGH_D_114122"],"award-info":[{"award-number":["TSGH_D_114122"]}],"id":[{"id":"https:\/\/ror.org\/007h4qe29","id-type":"ROR","asserted-by":"publisher"}]},{"award":["TSGH_E_115259"],"award-info":[{"award-number":["TSGH_E_115259"]}],"id":[{"id":"https:\/\/ror.org\/007h4qe29","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019000","name":"Ministry of National Defense-Medical Affairs Bureau","doi-asserted-by":"crossref","award":["MND-MAB-D-115119"],"award-info":[{"award-number":["MND-MAB-D-115119"]}],"id":[{"id":"10.13039\/501100019000","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Exosomes (Exos) derived from immune cells are emerging as potent drug delivery vectors. However, their biodistribution in clinically relevant lung cancer models remains underexplored. This study aimed to evaluate the lung-homing ability of NK cell Exos (NK-Exos) compared to mesenchymal stem cell Exos (MSC-Exos) in an orthotopic lung cancer model. Methods: Male SCID mice were orthotopically injected with luciferase-tagged A549 cells into the left lung to establish the tumor model. Mice were randomized into four groups: G1 (Healthy Control), G2 (Tumor Control + PBS), G3 (Tumor + DiR-labeled NK-Exos; 5 \u00b5M DiR + 5\u20137 \u00d7 109 Exo particles\/100 \u03bcL\/mouse), and G4 (Tumor + DiR-labeled MSC-Exos; 5 \u00b5M DiR + 5\u20137 \u00d7 109 Exo particles\/100 \u03bcL\/mouse). Six hours (15 min, 1 h, 2 h, 4 h, 6 h) post-intravenous injection, ex vivo biodistribution was assessed using the MILabs Spectrum imaging system. Results: Umbilical cord blood-NK-Exos (UCB-NK-Exos; G3) exhibited superior accumulation in lung tissues compared to UCB-MSC-Exos (G4), suggesting enhanced pulmonary retention. Intra-pulmonary analysis revealed an asymmetric distribution, with significantly higher radiant efficiency in the right lung (non-tumor bearing) compared to the left lung (tumor injection site) across Exo-treated groups. Conclusions: UCB-NK-Exos demonstrate distinct lung-targeting properties superior to MSC-Exos, supporting their potential as therapeutic carriers.<\/jats:p>","DOI":"10.3390\/life16040654","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T11:38:26Z","timestamp":1776080306000},"page":"654","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct Biodistribution of Natural Killer Cell-Derived Exosomes in an Orthotopic A549 Lung Cancer Mouse Model: Implications for Potent Targeted Drug Delivery"],"prefix":"10.3390","volume":"16","author":[{"given":"Yen-Lien","family":"Chou","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei 114202, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6883-1295","authenticated-orcid":false,"given":"Kuo-Feng","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical University, Taipei 114202, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0614-8854","authenticated-orcid":false,"given":"Ssu-Han","family":"Chen","sequence":"additional","affiliation":[{"name":"Department and Graduate Institute of Biochemistry, College of Biomedical Sciences, National Defense Medical University, Taipei 114201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7982-136X","authenticated-orcid":false,"given":"Shu-Yi","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy, National Defense Medical University, Taipei 114201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Kung","family":"Yeh","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy, National Defense Medical University, Taipei 114201, Taiwan"},{"name":"Graduate Institute of Life Sciences, National Defense Medical University, Taipei 114201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Kang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical University, Taipei 114202, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3783-4001","authenticated-orcid":false,"given":"Yuan-Ming","family":"Tsai","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical University, Taipei 114202, Taiwan"},{"name":"Department & Graduate Institute of Medical Education & Bioethics, National Taiwan University College of Medicine, Taipei 100233, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"ref_1","first-page":"17","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA A Cancer J. 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