{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:24:37Z","timestamp":1791815077146,"version":"4.3.4"},"reference-count":43,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Fund of Seoul St. Mary\u2019s Hospital, The Catholic University of Korea"},{"id":[{"id":"https:\/\/ror.org\/056cn0e37","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-00520440"],"award-info":[{"award-number":["RS-2025-00520440"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2025-00520440"],"award-info":[{"award-number":["RS-2025-00520440"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer (CRC), characterized by epidermal growth factor receptor (EGFR) overexpression, is often associated with poor prognosis and limited therapeutic response to conventional chemotherapy. In this study, we developed EGFR-targeted extracellular vesicles (EGFR-tEVs) by transiently engineering donor cells to display the GE11 peptide, aiming to enhance the precision of doxorubicin (Dox) delivery. The physicochemical properties of EGFR-tEVs were characterized using TEM, NTA, and Western blot. In vitro, EGFR-tEV-Dox exhibited increased cellular uptake in EGFR-overexpressing HCT-116 cells, leading to the activation of the p53-Bax-cleaved PARP1 apoptotic pathway. Notably, while Dox treatment induced p53 in normal colon fibroblasts (CCD18-Co), it did not trigger significant Bax activation or PARP1 cleavage, suggesting a preference for survival-related signaling in non-malignant cells. In a xenograft mouse model, EGFR-tEVs + Dox administration resulted in a 33.1% reduction in tumor volume and an 82.8% decrease in Ki-67 expression compared to the control group. These results indicate that transient receptor-mediated targeting enhances functional drug delivery to malignant tissues while minimizing pro-apoptotic induction in normal cells. Our findings suggest that EGFR-tEVs + Dox represents a balanced therapeutic strategy that improves antitumor efficacy with a favorable safety profile for EGFR-positive colorectal cancer.<\/jats:p>","DOI":"10.3390\/ijms27083693","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T16:10:44Z","timestamp":1776787844000},"page":"3693","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["EGFR-Targeted Extracellular Vesicles Potentiate Doxorubicin-Induced Apoptosis and Tumor Suppression in Colorectal Cancer"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4927-2754","authenticated-orcid":false,"given":"Chan Mi","family":"Lee","sequence":"first","affiliation":[{"name":"Central Institute of Surgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"},{"name":"Department of Surgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Won","family":"Choi","sequence":"additional","affiliation":[{"name":"Central Institute of Surgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do Sang","family":"Lee","sequence":"additional","affiliation":[{"name":"Central Institute of Surgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"},{"name":"Department of Surgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Won","family":"Moon","sequence":"additional","affiliation":[{"name":"Central Institute of Surgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6329-016X","authenticated-orcid":false,"given":"Jin Beom","family":"Cho","sequence":"additional","affiliation":[{"name":"Central Institute of Surgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"},{"name":"Division of Colorectal and Anorectal Surgery, Department of Surgery, Uijeongbu St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu 11765, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Hoon","family":"Bae","sequence":"additional","affiliation":[{"name":"Central Institute of Surgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"},{"name":"Department of Surgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1056\/NEJMra2200869","article-title":"Increasing incidence of early-onset colorectal cancer","volume":"386","author":"Sinicrope","year":"2022","journal-title":"N. 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