Mar 28, 2020

Redirected tropisms of extracellular vesicles and exomeres yield distinct biodistribution profiles

BioRxiv : the Preprint Server for Biology


Bionanoparticles including extracellular vesicles and exomeres (collectively termed EVs), have been shown to play significant roles in diseases and therapeutic applications. However, their spatiotemporal dynamics in vivo have remained largely unresolved in detail due to the lack of a suitable method. Here we report the development of a multi-resolution EV reporter, and reveal distinct biodistribution profiles following redirection of EV tropisms. We created a bioluminescence resonance energy transfer (BRET)-based reporter, PalmGRET, to enable pan-bionanoparticle labelling ranging from exomeres (< 50 nm) to small (< 200 nm) and medium and large (> 200 nm) EVs. PalmGRET emits robust, sustained signals and allows the visualization, tracking and quantification of bionanoparticles from whole-animal to nanoscopic resolutions under different imaging modalities, including bioluminescence, BRET and fluorescence. Using PalmGRET, we show that EVs released by lung metastatic hepatocellular carcinoma (HCC) exhibit lung tropism with varying distributions to other major organs in immunocompetent mice. EV proteomics identified HCC-EV lung tropic protein candidates associated with cancer progression, in which SLCO2A1 and CLIC1 expression on non...Continue Reading

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