{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:38:00Z","timestamp":1789616280344,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["678151"],"award-info":[{"award-number":["678151"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Membranes"],"abstract":"<jats:p>Cellular communications take place thanks to a well-connected network of chemical\u2013physical signals, biomolecules, growth factors, and vesicular messengers that travel inside or between cells. A deep knowledge of the extracellular vesicle (EV) system allows for a better understanding of the whole series of phenomena responsible for cell proliferation and death. To this purpose, here, a thorough immuno-phenotypic characterization of B-cell EV membranes is presented. Furthermore, the cellular membrane of B lymphocytes, Burkitt lymphoma, and human myeloid leukemic cells were characterized through cytofluorimetry assays and fluorescent microscopy analysis. Through cytotoxicity and internalization tests, the tropism of B lymphocyte-derived EVs was investigated toward the parental cell line and two different cancer cell lines. In this study, an innate capability of passive targeting of the native EVs was distinguished from the active targeting capability of monoclonal antibody-engineered EVs, able to selectively drive the vesicles, enhancing their internalization into the target cancer cells. In particular, the specific targeting ability of anti-CD20 engineered EVs towards Daudi cells, highly expressing CD20 marker on their cell membrane, was proved, while almost no internalization events were observed in HL60 cells, since they did not express an appreciable amount of the CD20 marker on their plasma membranes.<\/jats:p>","DOI":"10.3390\/membranes11110886","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T08:53:56Z","timestamp":1637225636000},"page":"886","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Extracellular Vesicles Tropism: A Comparative Study between Passive Innate Tropism and the Active Engineered Targeting Capability of Lymphocyte-Derived EVs"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5510-5561","authenticated-orcid":false,"given":"Tania","family":"Limongi","sequence":"first","affiliation":[{"name":"Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Susa","sequence":"additional","affiliation":[{"name":"Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Dumontel","sequence":"additional","affiliation":[{"name":"Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Racca","sequence":"additional","affiliation":[{"name":"Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Perrone Donnorso","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, 16132 Genova, Italy"},{"name":"Department of Pediatrics, IRCCS Istituto Giannina Gaslini, University of Genova, 16128 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doriana","family":"Debellis","sequence":"additional","affiliation":[{"name":"Electron Microscopy Laboratory, Center for Convergent Technologies, Istituto Italiano di Tecnologia (IIT), Via Morego 30, 16163 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2382-1533","authenticated-orcid":false,"given":"Valentina","family":"Cauda","sequence":"additional","affiliation":[{"name":"Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.3389\/fimmu.2019.02543","article-title":"Breast Milk-Derived Extracellular Vesicles Enriched in Exosomes From Mothers With Type 1 Diabetes Contain Aberrant Levels of microRNAs","volume":"10","author":"Mirza","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_2","first-page":"1","article-title":"Systems biology approaches to investigating the roles of extracellular vesicles in human diseases","volume":"51","author":"Visnovitz","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1656053","DOI":"10.1155\/2017\/1656053","article-title":"An Overview of Lipid Droplets in Cancer and Cancer Stem Cells","volume":"2017","author":"Tirinato","year":"2017","journal-title":"Stem Cells Int."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Susa, F., Limongi, T., Dumontel, B., Vighetto, V., and Cauda, V. (2019). Engineered Extracellular Vesicles as a Reliable Tool in Cancer Nanomedicine. Cancers, 11.","DOI":"10.3390\/cancers11121979"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Margolis, L., and Sadovsky, Y. (2019). The biology of extracellular vesicles: The known unknowns. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.3000363"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"22519","DOI":"10.1038\/srep22519","article-title":"Cells release subpopulations of exosomes with distinct molecular and biological properties","volume":"6","author":"Willms","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Witwer","year":"2018","journal-title":"J. Extracell. 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Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1172\/JCI81135","article-title":"The biology and function of exosomes in cancer","volume":"126","author":"Kalluri","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Conigliaro, A., and Cicchini, C. (2018). Exosome-Mediated Signaling in Epithelial to Mesenchymal Transition and Tumor Progression. J. Clin. Med., 8.","DOI":"10.3390\/jcm8010026"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/s41929-019-0333-4","article-title":"Cancer-derived exosomes loaded with ultrathin palladium nanosheets for targeted bioorthogonal catalysis","volume":"2","author":"Arruebo","year":"2019","journal-title":"Nat. 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Biopharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jconrel.2017.09.013","article-title":"Cancer-derived exosomes as a delivery platform of CRISPR\/Cas9 confer cancer cell tropism-dependent targeting","volume":"266","author":"Kim","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5681","DOI":"10.7150\/thno.34824","article-title":"Heterologous and cross-species tropism of cancer-derived extracellular vesicles","volume":"9","author":"Garofalo","year":"2019","journal-title":"Theranostics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1042\/BST20180253","article-title":"The role of extracellular vesicles in cancer microenvironment and metastasis: Myths and challenges","volume":"47","author":"Lucien","year":"2019","journal-title":"Biochem. Soc. Trans."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s12929-019-0500-6","article-title":"Cross-talk between cancer cells and their neighbors via miRNA in extracellular vesicles: An emerging player in cancer metastasis","volume":"26","author":"Kogure","year":"2019","journal-title":"J. Biomed. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1038\/s41467-020-14869-x","article-title":"Primary tumors release ITGBL1-rich extracellular vesicles to promote distal metastatic tumor growth through fibroblast-niche formation","volume":"11","author":"Ji","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1093\/carcin\/bgy115","article-title":"Colorectal cancer-derived small extracellular vesicles establish an inflammatory premetastatic niche in liver metastasis","volume":"39","author":"Shao","year":"2018","journal-title":"Carcinogenesis"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6975","DOI":"10.1038\/s41388-020-01514-6","article-title":"MCU-dependent negative sorting of miR-4488 to extracellular vesicles enhances angiogenesis and promotes breast cancer metastatic colonization","volume":"39","author":"Zheng","year":"2020","journal-title":"Oncogene"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1016\/j.ymthe.2018.07.023","article-title":"Exosome-Derived miR-130a Activates Angiogenesis in Gastric Cancer by Targeting C-MYBin Vascular Endothelial Cells","volume":"26","author":"Yang","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.virol.2019.07.024","article-title":"Expression of PD-1 and PD-Ls in Kaposi\u2019s sarcoma and regulation by oncogenic herpesvirus lytic reactivation","volume":"536","author":"Chen","year":"2019","journal-title":"Virology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e1062968","DOI":"10.1080\/2162402X.2015.1062968","article-title":"Hypoxic tumor-derived microvesicles negatively regulate NK cell function by a mechanism involving TGF-\u03b2 and miR23a transfer","volume":"5","author":"Berchem","year":"2015","journal-title":"Oncoimmunology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2732","DOI":"10.7150\/thno.18752","article-title":"Exosomes Derived From Natural Killer Cells Exert Therapeutic Effect in Melanoma","volume":"7","author":"Zhu","year":"2017","journal-title":"Theranostics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1002\/ijc.31792","article-title":"Prodrug suicide gene therapy for cancer targeted intracellular by mesenchymal stem cell exosomes","volume":"144","author":"Altanerova","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e1071008","DOI":"10.1080\/2162402X.2015.1071008","article-title":"Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC","volume":"5","author":"Besse","year":"2015","journal-title":"Oncoimmunology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1016\/j.ymthe.2017.02.007","article-title":"Exosomes from M1-Polarized Macrophages Potentiate the Cancer Vaccine by Creating a Pro-inflammatory Microenvironment in the Lymph Node","volume":"25","author":"Cheng","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_31","first-page":"3.22.21","article-title":"Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids","volume":"30","author":"Amigorena","year":"2006","journal-title":"Curr. Protoc. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"19861","DOI":"10.3402\/jev.v2i0.19861","article-title":"How pure are your vesicles?","volume":"2","author":"Webber","year":"2013","journal-title":"J. Extracell. Vesicles"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1002\/cyto.a.24193","article-title":"Evaluation of Exosome Proteins by on-Bead Flow Cytometry","volume":"99","author":"Theodoraki","year":"2020","journal-title":"Cytom. Part A"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6391264","DOI":"10.1155\/2016\/6391264","article-title":"Phenotyping of Leukocytes and Leukocyte-Derived Extracellular Vesicles","volume":"2016","author":"Pugholm","year":"2016","journal-title":"J. Immunol. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1016\/j.biopha.2018.11.121","article-title":"The applications of anti-CD20 antibodies to treat various B cells disorders","volume":"109","author":"Payandeh","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1038\/sj.leu.2402639","article-title":"Anti-CD20-based therapy of B cell lymphoma: State of the art","volume":"16","author":"Kosmas","year":"2002","journal-title":"Leukemia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/978-3-319-73670-9_43","article-title":"Rituximab-related Severe Toxicity","volume":"2018","author":"Ghrenassia","year":"2018","journal-title":"Annu. Update Intensive Care Emerg. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3389\/fonc.2018.00163","article-title":"Past, Present, and Future of Rituximab\u2014The World\u2019s First Oncology Monoclonal Antibody Therapy","volume":"8","author":"Pierpont","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1182\/blood-2004-01-0277","article-title":"Rituximab antiproliferative effect in B-lymphoma cells is associated with acid-sphingomyelinase activation in raft microdomains","volume":"104","author":"Bezombes","year":"2004","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.critrevonc.2015.09.001","article-title":"A molecular perspective on rituximab: A monoclonal antibody for B cell non Hodgkin lymphoma and other affections","volume":"97","author":"Seyfizadeh","year":"2016","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2954","DOI":"10.1016\/j.bbamem.2014.07.026","article-title":"Examination of the specificity of tumor cell derived exosomes with tumor cells in vitro","volume":"1838","author":"Smyth","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"533","DOI":"10.3389\/fphar.2016.00533","article-title":"Exosome-Based Cancer Therapy: Implication for Targeting Cancer Stem Cells","volume":"7","author":"Wang","year":"2017","journal-title":"Front. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nature15756","article-title":"Tumour exosome integrins determine organotropic metastasis","volume":"527","author":"Hoshino","year":"2015","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-019-0223-5","article-title":"Extracellular vesicle-based therapeutics: Natural versus engineered targeting and trafficking","volume":"51","author":"Murphy","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s00018-017-2664-0","article-title":"Amyloid precursor protein products concentrate in a subset of exosomes specifically endocytosed by neurons","volume":"75","author":"Laulagnier","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.bbrc.2017.05.049","article-title":"Fibronectin on extracellular vesicles from microvascular endothelial cells is involved in the vesicle uptake into oligodendrocyte precursor cells","volume":"488","author":"Osawa","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.xphs.2016.07.022","article-title":"Role of Phosphatidylserine-Derived Negative Surface Charges in the Recognition and Uptake of Intravenously Injected B16BL6-Derived Exosomes by Macrophages","volume":"106","author":"Matsumoto","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.bbrc.2017.07.126","article-title":"Glycan profiling analysis using evanescent-field fluorescence-assisted lectin array: Importance of sugar recognition for cellular uptake of exosomes from mesenchymal stem cells","volume":"491","author":"Shimoda","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1446660","DOI":"10.1080\/20013078.2018.1446660","article-title":"Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8","volume":"7","author":"Berenguer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4552","DOI":"10.1039\/D0TB00744G","article-title":"Surface functionalization strategies of extracellular vesicles","volume":"8","author":"Rayamajhi","year":"2020","journal-title":"J. Mater. Chem. B"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"16413","DOI":"10.1021\/jacs.8b10047","article-title":"Reprogramming Exosomes as Nanoscale Controllers of Cellular Immunity","volume":"140","author":"Cheng","year":"2018","journal-title":"J. Am. Chem. Soc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1158\/1535-7163.MCT-17-0827","article-title":"Anti-HER2 scFv-Directed Extracellular Vesicle-Mediated mRNA-Based Gene Delivery Inhibits Growth of HER2-Positive Human Breast Tumor Xenografts by Prodrug Activation","volume":"17","author":"Wang","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1039\/C7NR06966A","article-title":"Recombinant phosphatidylserine-binding nanobodies for targeting of extracellular vesicles to tumor cells: A plug-and-play approach","volume":"10","author":"Kooijmans","year":"2018","journal-title":"Nanoscale"}],"container-title":["Membranes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0375\/11\/11\/886\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:32:01Z","timestamp":1760167921000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0375\/11\/11\/886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,18]]},"references-count":53,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["membranes11110886"],"URL":"https:\/\/doi.org\/10.3390\/membranes11110886","relation":{},"ISSN":["2077-0375"],"issn-type":[{"value":"2077-0375","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,18]]}}}