期刊
JOURNAL OF EXTRACELLULAR VESICLES
卷 4, 期 -, 页码 -出版社
TAYLOR & FRANCIS LTD
DOI: 10.3402/jev.v4.26316
关键词
biodistribution; drug delivery; exosomes; extracellular vesicles; microvesicles; nanotechnology; tissue targeting
类别
资金
- Swedish Research Council (VR-Med)
- Swedish Research Council (EuroNanoMedII)
- Swedish Cancer Society
- Swedish Society of Medical Research (SSMF)
- Karolinska Institutet
- Wellcome Trust
- Agency for Science, Technology and Research (A*STAR), Singapore
- Postdoctoral MOBILITAS Fellowship of the Estonian Science Foundation
- EU IMI (Innovative Medicines Initiative) project COMPACT (Collaboration on the optimisation of macromolecular pharmaceutical access to cellular targets)
- national scholarship program Kristjan Jaak - Archimedes Foundation
- Estonian Ministry of Education and Research
- Swedish Research Council [VR K2014-64X-20742-07-5]
- Vinnova [2010-00501]
- Parkinson"
- s UK [G-1109] Funding Source: researchfish
Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in a diverse range of biological processes. For future therapeutic applications and for EV biology research in general, understanding the in vivo fate of EVs is of utmost importance. Here we studied biodistribution of EVs in mice after systemic delivery. EVs were isolated from 3 different mouse cell sources, including dendritic cells (DCs) derived from bone marrow, and labelled with a near-infrared lipophilic dye. Xenotransplantation of EVs was further carried out for cross-species comparison. The reliability of the labelling technique was confirmed by sucrose gradient fractionation, organ perfusion and further supported by immunohistochemical staining using CD63-EGFP probed vesicles. While vesicles accumulated mainly in liver, spleen, gastrointestinal tract and lungs, differences related to EV cell origin were detected. EVs accumulated in the tumour tissue of tumour-bearing mice and, after introduction of the rabies virus glycoprotein-targeting moiety, they were found more readily in acetylcholine-receptor-rich organs. In addition, the route of administration and the dose of injected EVs influenced the biodistribution pattern. This is the first extensive biodistribution investigation of EVs comparing the impact of several different variables, the results of which have implications for the design and feasibility of therapeutic studies using EVs.
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