Abstract
Background and Aims: Existing delivery vehicles are associated with concerns about toxicity and whether specific tissues are appropriately targeted. Exosomes are natural cell-derived nanocarriers that have the intrinsic ability to cross biological barriers. In the present study, we characterized liver exosomes and their tissue-targeting properties. Methods: Liver and colon cultures derived from 6 week-old (C57BL/6) mice were grown in conditioned media and exosome release was evaluated using differential high speed ultracentrifugation. Exosomes size and morphology were assessed employing light-scattering techniques, atomic force microscopy, and scanning electron microscopy. The exosomal marker CD63 was used to assess the purity of exosome preparations. As exosomes contain esterase, isolated exosomes were labeled with a fluorescent probe (BCECF AM, 5μM) or with CD98 siRNA and injected intraperitoneally into healthy mice (C57BL/6). Two hours later, the mice were humanely euthanized and the levels of labeled exosomes were measured in the liver, colon, and spleen. Results: The liver released vesicles were 80-150 nm in diameter bearing the exosomal marker CD63. Labeled liver exosomes injected into mice accumulated almost exclusively in the liver (87%), being minimally present in colon and spleen tissues (less than 2%). In contrast, when labeled exosomes secreted from colon tissue were injected, 70% were found in colon tissue, 5% in the spleen, and 4% in the liver. I.P. injection of exosomes loaded CD98 siRNA showed a downregulation in their original organs. Liver extracted exosomes downregulated 78% of the CD98 expression compared to 17% in the colon. Interestingly, exosomes extracted from the colon downregulated 69% of the CD98 expression on the colon versus 3% in the liver. Conclusion: Injected liver and colon exosomes specifically target the tissue of origin. Exosomes may be used as natural targeted nanocarriers for drug delivery.
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