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

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 131 I-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. Exosomes are biological nanoparticles, which have immense prospects for clinical application as a diagnostic marker, monitoring disease progression and potential therapeutic carrier. However, this advancement has been impaired by lacking of optimized isolation method and inadequate techniques to track their in vivo distribution. Here we present a simple, rapid and high yielding exosome isolation technique utilizing a combination of size-based and ultracentrifugation method. We also demonstrated the exact visualization and quantification of radioisotope-labeled exosomes from different cell types with or without treatment, in the primary solid tumors and metastatic area, which are dependent on the protein/cytokine contents of the exosomes.