{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:40:13Z","timestamp":1787636413943,"version":"build-2736575974"},"reference-count":67,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA1101500"],"award-info":[{"award-number":["2021YFA1101500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92049119"],"award-info":[{"award-number":["92049119"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81974009"],"award-info":[{"award-number":["81974009"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471838"],"award-info":[{"award-number":["82471838"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Engineered extracellular vesicles (EVs) are emerging as a highly potential platform for targeted drug delivery in cancer therapy. Although intravenous injection is commonly used in EV treatment, there is growing interest in using microneedles (MNs) for transdermal EV delivery; however, comprehensive studies comparing the tissue distribution, safety and antitumour efficacy of these two approaches for delivering engineered EVs remain scarce.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used EVs derived from umbilical cord mesenchymal stem cells, modified with phospholipid\u2012polyethylene glycol\u2012N\u2010hydroxysuccinimide and conjugated with CD38 peptides (CD38\u2010EVs), to target myeloma cells that highly express CD38 antigen, and tested their safety and antitumour efficacy in mice with subcutaneous plasmacytoma, administrated via dissolvable transdermal MNs or intravenous injection. Flow cytometry, immunofluorescence and fluorescence molecular projection imaging analysis were employed to evaluate the distribution of CD38\u2010EVs at the cellular level and within living systems. Additionally, histopathological analysis and biochemical analyses were conducted to assess the antitumour effects and safety of CD38\u2010EVs loaded with doxorubicin (CD38\u2010EVs\u2010Dox).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to standard EVs, CD38\u2010EVs exhibited enhanced uptake by CD38<jats:sup>high<\/jats:sup> tumour cells and reduced uptake by CD38\u2010negative non\u2010tumour cells in vitro. In plasmacytoma NOD\/SCID mouse models, CD38\u2010EVs encapsulated within MNs (CD38\u2010EVs<jats:sup>MNs<\/jats:sup>) effectively targeted the tumour cells much more than the standard EVs encapsulated within MNs (EVs<jats:sup>MNs<\/jats:sup>) and CD38\u2010EVs intravenously administrated (CD38\u2010EVs<jats:sup>i.v<\/jats:sup>), with reduced distribution to the lungs and spleen. Additionally, CD38\u2010EVs\u2010Dox induced significantly greater cytotoxicity against the tumour cells than EVs\u2010Dox in vitro, and CD38\u2010EVs\u2010Dox<jats:sup>MNs<\/jats:sup> significantly reduced tumour burden compared to both EVs\u2010Dox<jats:sup>MNs<\/jats:sup> and CD38\u2010EVs\u2010Dox<jats:sup>i.v<\/jats:sup>, while maintaining favourable safety profiles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>CD38\u2010EVs\u2010Dox<jats:sup>MNs<\/jats:sup> have superior efficacy and safety in treating plasmacytoma mice, compared to CD38\u2010EVs\u2010Dox<jats:sup>i.v<\/jats:sup>, providing novel insights into the potential of MNs as a platform for delivering targeted engineered EVs in tumour therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>Enhanced tumor targeting<\/jats:bold>: CD38\u2010modified EVs (CD38\u2010EVs) showed increased uptake by CD38high tumor cells while reducing uptake by CD38\u2010negative non\u2010tumor cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>Optimized delivery<\/jats:bold>: MN\u2010loaded CD38\u2010EVs targeted tumors more effectively than MN\u2010loaded EVs and intravenously injected CD38\u2010EVs, with lower lung and spleen accumulation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>Superior antitumor efficacy<\/jats:bold>: MN\u2010delivered CD38\u2010EVs\u2010Dox significantly suppressed tumor growth, outperforming intravenous CD38\u2010EVs\u2010Dox and MN\u2010delivered EVs\u2010Dox.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.70327","type":"journal-article","created":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T00:18:22Z","timestamp":1746231502000},"source":"Crossref","is-referenced-by-count":7,"title":["Targeting capacity, safety and efficacy of engineered extracellular vesicles delivered by transdermal microneedles to treat plasmacytoma in mice"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2933-7796","authenticated-orcid":false,"given":"Yulin","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Hematology Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 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