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However, native EVs primarily accumulate in liver, spleen and lungs, limiting targeted delivery to disease sites. To enhance their targeting efficiency for the plasma cell cancer multiple myeloma (MM), localized in the bone marrow (BM), we engineered HEK293\u2010derived EVs to display a nanobody (Nb) against the MM cell surface marker CS1. We confirmed enrichment of the Nb construct on engineered EVs and binding of \u03b1\u2010CS1 EVs to CS1.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , we found enhanced \u03b1\u2010CS1 EV uptake by MM cell cultures.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , we first compared the biodistribution of HEK293\u2010derived native EVs in healthy and MM\u2010bearing mice. Although native EVs reached the BM in both groups, MM\u2010bearing mice showed increased liver and lung accumulation together with reduced BM delivery. \u03b1\u2010mCS1 EV delivery to the BM of MM\u2010bearing mice was only slightly increased compared to native EVs, while off\u2010target accumulation also increased. At the cellular level, no changes in EV delivery to MM cells were detected. In conclusion, while CS1 targeting enhances\n                    <jats:italic>in vitro<\/jats:italic>\n                    EV uptake by MM cells,\n                    <jats:italic>in vivo<\/jats:italic>\n                    biodistribution remains suboptimal. Further optimization is needed to improve EV\u2010based drug delivery for MM.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70325","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T05:19:01Z","timestamp":1781759941000},"source":"Crossref","is-referenced-by-count":0,"title":["Characterizing the Fate of Anti\u2010CS1 Nanobody Displaying Extracellular Vesicles in Multiple Myeloma"],"prefix":"10.1002","volume":"15","author":[{"given":"Michiel","family":"De Coster","sequence":"first","affiliation":[{"name":"Translational Oncology Research Center (TORC), Team Hematology and Immunology (HEIM) Vrije Universiteit Brussel  Brussels Belgium"},{"name":"Laboratory for Extracellular Vesicle Research, Department of Human Genetics Katholieke Universiteit Leuven  Leuven 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(HEIM) Vrije Universiteit Brussel  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline","family":"Menu","sequence":"additional","affiliation":[{"name":"Translational Oncology Research Center (TORC), Team Hematology and Immunology (HEIM) Vrije Universiteit Brussel  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8768-1790","authenticated-orcid":false,"given":"Pascale","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Laboratory for Extracellular Vesicle Research, Department of Human Genetics Katholieke Universiteit Leuven  Leuven Belgium"},{"name":"\u00c9quipe Labellis\u00e9e Ligue 2018, INSERM 1068, CNRS 7258, Institut Paoli Calmettes, Centre de Recherche en Canc\u00e9rologie de Marseille Aix Marseille Universit\u00e9  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4012-4617","authenticated-orcid":false,"given":"Elke","family":"De Bruyne","sequence":"additional","affiliation":[{"name":"Translational Oncology Research Center (TORC), Team Hematology and Immunology (HEIM) Vrije Universiteit Brussel  Brussels 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