Abstract
Exosomes are produced by cells to mediate intercellular communication, and have been shown to perpetuate diseases, including cancer. New tools are needed to understand exosome biology, detect exosomes from specific cell types in complex biological media, and to modify exosomes. Our data demonstrate a cellular pathway whereby membrane-bound scavenger receptor type B-1 (SR-B1) in parent cells becomes incorporated into exosomes. We tailored synthetic HDL-like nanoparticles (HDL NP), high-affinity ligands for SR-B1, to carry a fluorescently labeled phospholipid. Data show SR-B1-dependent transfer of the fluorescent phospholipid from HDL NPs to exosomes. Modified exosomes are stable in serum and can be directly detected using flow cytometry. As proof-of-concept, human serum exosomes were found to express SR-B1, and HDL NPs can be used to label and isolate them. Ultimately, we discovered a natural cellular pathway and nanoparticle-receptor pair that enables exosome modulation, detection, and isolation.
Highlights
A tailorable, synthetic ligand would identify a natural pathway of exosome production and a way to modulate exosome cargo
scavenger receptor type B-1 (SR-B1) is present in exosomes obtained from the serum of patients with melanoma, which allows for labeling and isolation of the exosomes using Rh-high-density lipoproteins (HDL) nanoparticle (HDL NP)
Having determined that the Rh-HDL NPs associate with exosomes, we investigated whether the exosomes isolated from conditioned media of CWR22Rv1 cells exhibited rhodamine fluorescence
Summary
A tailorable, synthetic ligand would identify a natural pathway of exosome production and a way to modulate exosome cargo. Uptake of Rh-HDL NPs by CWR22Rv1 cells was confirmed by flow cytometry (Supplementary Fig. S2). Having determined that the Rh-HDL NPs associate with exosomes, we investigated whether the exosomes isolated from conditioned media of CWR22Rv1 cells exhibited rhodamine fluorescence.
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