Efficient production and enhanced tumor delivery of engineered extracellular vesicles

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dc.citation.epage205en_US
dc.citation.spage195en_US
dc.citation.volumeNumber105en_US
dc.contributor.authorWatson, D. C.en_US
dc.contributor.authorBayik D.en_US
dc.contributor.authorSrivatsan, A.en_US
dc.contributor.authorBergamaschi, C.en_US
dc.contributor.authorValentin, A.en_US
dc.contributor.authorNiu, G.en_US
dc.contributor.authorBear, J.en_US
dc.contributor.authorMonninger, M.en_US
dc.contributor.authorSun, M.en_US
dc.contributor.authorMorales-Kastresana, A.en_US
dc.contributor.authorJones, J. C.en_US
dc.contributor.authorFelber, B. K.en_US
dc.contributor.authorChen, X.en_US
dc.contributor.authorGurse,l I.en_US
dc.contributor.authorPavlakis, G. N.en_US
dc.date.accessioned2018-04-12T10:56:08Z
dc.date.available2018-04-12T10:56:08Z
dc.date.issued2016en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractExtracellular vesicles (EV), including exosomes and microvesicles, are nano-sized intercellular communication vehicles that participate in a multitude of physiological processes. Due to their biological properties, they are also promising candidates for the systemic delivery of therapeutic compounds, such as cytokines, chemotherapeutic drugs, siRNAs and viral vectors. However, low EV production yield and rapid clearance of administered EV by liver macrophages limit their potential use as therapeutic vehicles. We have used a hollow-fiber bioreactor for the efficient production of bioactive EV bearing the heterodimeric cytokine complex Interleukin-15:Interleukin-15 receptor alpha. Bioreactor culture yielded ∼40-fold more EV per mL conditioned medium, as compared to conventional cell culture. Biophysical analysis and comparative proteomics suggested a more diverse population of EV in the bioreactor preparations, while serum protein contaminants were detectable only in conventional culture EV preparations. We also identified the Scavenger Receptor Class A family (SR-A) as a novel monocyte/macrophage uptake receptor for EV. In vivo blockade of SR-A with dextran sulfate dramatically decreased EV liver clearance in mice, while enhancing tumor accumulation. These findings facilitate development of EV therapeutic methods. © 2016en_US
dc.identifier.doi10.1016/j.biomaterials.2016.07.003en_US
dc.identifier.issn0142-9612
dc.identifier.urihttp://hdl.handle.net/11693/36872
dc.language.isoEnglishen_US
dc.publisherElsevier Ltden_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.biomaterials.2016.07.003en_US
dc.source.titleBiomaterialsen_US
dc.subjectBiodistributionen_US
dc.subjectDextran sulfateen_US
dc.subjectDrug deliveryen_US
dc.subjectExosomesen_US
dc.subjectReticuloendothelial systemen_US
dc.subjectScavenger receptoren_US
dc.titleEfficient production and enhanced tumor delivery of engineered extracellular vesiclesen_US
dc.typeArticleen_US

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