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      Folate-displaying exosome mediated cytosolic delivery of siRNA avoiding endosome trapping

      , , , ,
      Journal of Controlled Release
      Elsevier BV

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          Abstract

          Folate (FA) receptor is a cell surface glycoprotein overexpressed on many cancer cells. It is a high affinity ligand for cancer cell targeting. However, delivery of siRNA directly through folate receptor mediated endocytosis for gene silencing has not, if any, been successful in cell culture, animal models or clinical trial. We have reported the application of RNA nanotechnology to construct FA-displaying exosomes for efficient cell targeting, siRNA delivery and cancer regression (Pi et.al Nature Nanotechnology, 2018:13, 82–89; Li et.al., Scientific Report, 2018:8, 14644). However, the mechanism underlying the efficient therapeutic behavior through folate/exosome complex remains elusive. Here we demonstrate that the efficient cancer suppression with the FA-displaying exosome was due to the receptor-mediated cytosol delivery of the siRNA payload without endosome trapping, as attested by fluorescence colocalization analysis, gene knockdown assay and animal tumor regression. It is expected that the high potency of FA-displaying exosome in cytosolic siRNA delivery will renew the concept and interest in using FA as cancer targeting ligand in human cancer therapy.

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          Author and article information

          Journal
          Journal of Controlled Release
          Journal of Controlled Release
          Elsevier BV
          01683659
          August 2019
          August 2019
          Article
          10.1016/j.jconrel.2019.08.021
          6874920
          31446085
          ade90415-b3e6-4463-afe5-2ed54c4b8a10
          © 2019

          https://www.elsevier.com/tdm/userlicense/1.0/

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