{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T07:54:01Z","timestamp":1793606041947,"version":"4.5.0"},"reference-count":51,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Korean government (MSIP)","doi-asserted-by":"publisher","award":["NRF-2020R1A2C1099712"],"award-info":[{"award-number":["NRF-2020R1A2C1099712"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korean government (MSIP)","doi-asserted-by":"publisher","award":["RS-2024-00334734"],"award-info":[{"award-number":["RS-2024-00334734"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Exosomes are nanosized extracellular vesicles secreted by various cells, including natural killer (NK) cells, and are known for their low toxicity, high permeability, biocompatibility, and strong targeting ability. NK cell-derived exosomes (NK-exos) contain cytotoxic proteins that enhance tumor-targeting efficiency, making them suitable for treating solid tumors such as hepatocellular carcinoma (HCC). Despite their potential in drug delivery, the mechanisms of drug-loaded NK-exos, particularly those loaded with doxorubicin (NK-exos-Dox), remain unclear in HCC. This study explored the anti-tumor effects of NK-exos-Dox against Hep3B cells in vitro. NK-exos-Dox expressed exosome markers (CD9 and CD63) and cytotoxic proteins (granzyme B and perforin) and measured 170\u2013220 nm in size. Compared to NK-exos, NK-exos-Dox enhanced cytotoxicity and apoptosis in Hep3B cells by upregulating pro-apoptotic proteins (Bax, cytochrome c, cleaved caspase 3, and cleaved PARP) and inhibiting the anti-apoptotic protein (Bcl-2). These findings suggest that NK-exos-Dox significantly boost anti-tumor effects by activating specific cytotoxic molecules, offering promising therapeutic opportunities for solid tumor treatment, including HCC.<\/jats:p>","DOI":"10.3390\/ijms26052234","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T05:52:16Z","timestamp":1740981136000},"page":"2234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Enhanced Anti-Tumor Effects of Natural Killer Cell-Derived Exosomes Through Doxorubicin Delivery to Hepatocellular Carcinoma Cells: Cytotoxicity and Apoptosis Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2783-2291","authenticated-orcid":false,"given":"You Hee","family":"Choi","sequence":"first","affiliation":[{"name":"Korea Institute of Medical Microrobotics, 43-26 Cheomdangwagi-ro, Buk-gu, Gwangju 61011, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8187-5666","authenticated-orcid":false,"given":"Ho Yong","family":"Kim","sequence":"additional","affiliation":[{"name":"Korea Institute of Medical Microrobotics, 43-26 Cheomdangwagi-ro, Buk-gu, Gwangju 61011, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Oh","family":"Park","sequence":"additional","affiliation":[{"name":"Korea Institute of Medical Microrobotics, 43-26 Cheomdangwagi-ro, Buk-gu, Gwangju 61011, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9689-6520","authenticated-orcid":false,"given":"Eunpyo","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Sogang University, 35, Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.2147\/JHC.S61146","article-title":"Hepatocellular carcinoma: A review","volume":"3","author":"Balogh","year":"2016","journal-title":"J. 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