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


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 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, 14,644). 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.

SUBMITTER: Zheng Z 

PROVIDER: S-EPMC6874920 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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

Zheng Zhen Z   Li Zhefeng Z   Xu Congcong C   Guo Bin B   Guo Peixuan P  

Journal of controlled release : official journal of the Controlled Release Society 20190822


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 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, 82-8  ...[more]

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