Frontiers in Molecular Biosciences (Sep 2021)

Delivery of Anti-miRNA-221 for Colorectal Carcinoma Therapy Using Modified Cord Blood Mesenchymal Stem Cells-Derived Exosomes

  • Siqi Han,
  • Siqi Han,
  • Siqi Han,
  • Guangchao Li,
  • Meng Jia,
  • Yulu Zhao,
  • Chenglong He,
  • Mengxi Huang,
  • Longwei Jiang,
  • Meijuan Wu,
  • Jiahe Yang,
  • Xiaoqin Ji,
  • Xiaobei Liu,
  • Cheng Chen,
  • Cheng Chen,
  • Cheng Chen,
  • Xiaoyuan Chu,
  • Xiaoyuan Chu,
  • Xiaoyuan Chu

DOI
https://doi.org/10.3389/fmolb.2021.743013
Journal volume & issue
Vol. 8

Abstract

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Background: Exosomes, as natural intercellular information carriers, have great potential in the field of drug delivery. Many studies have focused on modifying exosome surface proteins to allow drugs to specifically target cancer cells.Methods: In this study, human cord blood mesenchymal stromal cell-derived exosomes were used in the delivery of anti-miRNA oligonucleotides so as to be specifically ingested by tumor cells to perform anti-tumor functions. Mesenchymal stem cells modified by the fusion gene iRGD-Lamp2b were constructed to separate and purify exosomes, and the anti-miRNA-221 oligonucleotide (AMO) was loaded into the exosomes by electroporation.Results: The AMO-loaded exosomes (AMO-Exos) effectively inhibited the proliferation and clonal formation of colon cancer cells in vitro, and it was further found that AMO-Exos was taken up by tumor cells through interaction with the NRP-1 protein. The results of a xenograft tumor model also showed that iRGD-modified exosomes were obviously enriched in tumor sites, exerting excellent anti-tumor efficacy. In vivo imaging showed that exosomes were mainly distributed in liver, spleen, and lung tissues.Conclusion: Our results suggest that genetically modified exosomes could be an ideal natural nanostructure for anti-miRNA oligonucleotide delivery.

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