Differential in vivo biodistribution of 131I-labeled exosomes from diverse cellular origins and its implication for theranostic application

• Type of Material: Article
• Authors: Mohammad H. Rashid, Augusta University; Thaiz F. Borin, Augusta University; Roxan Ara, Augusta University; Kartik Angara, Michigan State University; Jingwen Cai, Medical College of Georgia; Bhagelu R. Achyut, Emory University; Yutao Liu, Medical College of Georgia; Ali S. Arbab, Augusta University
• Language: English
• Date: 2019-10-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 The Author(s). Published by Elsevier Inc.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.nano.2019.102072
• Title of Journal or Parent Work: Nanomedicine: Nanotechnology, Biology, and Medicine
• Volume: 21
• Start Page: 102072
• End Page: 102072
• Grant/Funding Information: National Institutes of Health (NIH) grant R01CA160216, Startup funding from Georgia Cancer Center, American Cancer Society grant IRG-14-193-01 to Dr. Bhagelu R. Achyut.
• Keywords: Theranostic Nanomedicine; Organ Specificity; Iodine Radioisotopes; EPC exosomes; Animals; Exosomes; Mice; Radioisotope labeling; in vivo imaging; Isotope Labeling; MDSC exosomes; Mice, Inbred BALB C; Isolation; Cell Line

Abstract

Exosomes are critical mediators of intercellular crosstalk and are regulator of the cellular/tumor microenvironment. Exosomes have great prospects for clinical application as a theranostic and prognostic probe. Nevertheless, the advancement of exosomes research has been thwarted by our limited knowledge of the most efficient isolation method and their in vivo trafficking. Here we have shown that a combination of two size-based methods using a 0.20 μm syringe filter and 100 k centrifuge membrane filter followed by ultracentrifugation yields a greater number of uniform exosomes. We also demonstrated the visual representation and quantification of the differential in vivo distribution of radioisotope 131I-labeled exosomes from diverse cellular origins, e.g., tumor cells with or without treatments, myeloid-derived suppressor cells and endothelial progenitor cells. We also determined that the distribution was dependent on the exosomal protein/cytokine contents. The applied in vivo imaging modalities can be utilized to monitor disease progression, metastasis, and exosome-based targeted therapy.