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Here, we developed a drug delivery system utilizing 293T cell\u2010derived extracellular vesicles (EVs) modified with an anti\u2010CD7 single\u2010chain variable fragment (\u03b1CD7\/EVs). Given the challenges of chemotherapy resistance in patients with T\u2010cell malignancy, we selected cytochrome C (CytC) and <jats:italic>Bcl2<\/jats:italic> siRNA (<jats:italic>siBcl2<\/jats:italic>) as therapeutic agents and loaded them into \u03b1CD7\/EVs (\u03b1CD7\/EVs\/CytC\/<jats:italic>siBcl2<\/jats:italic>). We found that \u03b1CD7\/EVs efficiently targeted and were internalized by human T\u2010ALL Molt\u20104 cells. In addition, the interaction between \u03b1CD7 and CD7 switched the EV entry pathway in Molt\u20104 cells from macropinocytosis\u2010dependent endocytosis to clathrin\u2010mediated endocytosis, thereby reducing EV\u2010lysosome colocalization, ultimately improving CytC delivery efficiency and increasing the cytotoxicity of nascent EVs from EV\u2010treated Molt\u20104 cells. Notably, \u03b1CD7\/EVs\/CytC\/<jats:italic>siBcl2<\/jats:italic> demonstrated similar efficacy against both Molt\u20104 and chemotherapy\u2010resistant Molt\u20104 cells (CR\u2010Molt\u20104). Furthermore, \u03b1CD7\/EVs\/CytC\/<jats:italic>siBcl2<\/jats:italic> exhibited high safety, low immunogenicity and minimal impact on human T cells. Therefore, \u03b1CD7\/EVs\/CytC\/<jats:italic>siBcl2<\/jats:italic> are promising therapeutic approaches for treating CD7<jats:sup>+<\/jats:sup> T\u2010cell malignancies.<\/jats:p>","DOI":"10.1002\/jev2.70025","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T05:44:16Z","timestamp":1734327856000},"source":"Crossref","is-referenced-by-count":8,"title":["CD7\u2010targeting pro\u2010apoptotic extracellular vesicles: A novel approach for T\u2010cell haematological malignancy therapy"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1090-4763","authenticated-orcid":false,"given":"Bei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics of the Second Affiliated Hospital and Institute of Immunology Zhejiang University School of Medicine Hangzhou China"},{"name":"Department of Blood Transfusion The First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 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Hospital Medical School of Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health National Children\u2019s Regional Medical Center  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics of the Second Affiliated Hospital and Institute of Immunology Zhejiang University School of Medicine Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou 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