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Delivery of Anti-miRNA-221 for Colorectal Carcinoma Therapy Using Modified Cord Blood Mesenchymal Stem Cells-Derived Exosomes
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 ce...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488275/ https://www.ncbi.nlm.nih.gov/pubmed/34616773 http://dx.doi.org/10.3389/fmolb.2021.743013 |
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author | Han, Siqi Li, Guangchao Jia, Meng Zhao, Yulu He, Chenglong Huang, Mengxi Jiang, Longwei Wu, Meijuan Yang, Jiahe Ji, Xiaoqin Liu, Xiaobei Chen, Cheng Chu, Xiaoyuan |
author_facet | Han, Siqi Li, Guangchao Jia, Meng Zhao, Yulu He, Chenglong Huang, Mengxi Jiang, Longwei Wu, Meijuan Yang, Jiahe Ji, Xiaoqin Liu, Xiaobei Chen, Cheng Chu, Xiaoyuan |
author_sort | Han, Siqi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8488275 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84882752021-10-05 Delivery of Anti-miRNA-221 for Colorectal Carcinoma Therapy Using Modified Cord Blood Mesenchymal Stem Cells-Derived Exosomes Han, Siqi Li, Guangchao Jia, Meng Zhao, Yulu He, Chenglong Huang, Mengxi Jiang, Longwei Wu, Meijuan Yang, Jiahe Ji, Xiaoqin Liu, Xiaobei Chen, Cheng Chu, Xiaoyuan Front Mol Biosci Molecular Biosciences 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. Frontiers Media S.A. 2021-09-20 /pmc/articles/PMC8488275/ /pubmed/34616773 http://dx.doi.org/10.3389/fmolb.2021.743013 Text en Copyright © 2021 Han, Li, Jia, Zhao, He, Huang, Jiang, Wu, Yang, Ji, Liu, Chen and Chu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Han, Siqi Li, Guangchao Jia, Meng Zhao, Yulu He, Chenglong Huang, Mengxi Jiang, Longwei Wu, Meijuan Yang, Jiahe Ji, Xiaoqin Liu, Xiaobei Chen, Cheng Chu, Xiaoyuan Delivery of Anti-miRNA-221 for Colorectal Carcinoma Therapy Using Modified Cord Blood Mesenchymal Stem Cells-Derived Exosomes |
title | Delivery of Anti-miRNA-221 for Colorectal Carcinoma Therapy Using Modified Cord Blood Mesenchymal Stem Cells-Derived Exosomes |
title_full | Delivery of Anti-miRNA-221 for Colorectal Carcinoma Therapy Using Modified Cord Blood Mesenchymal Stem Cells-Derived Exosomes |
title_fullStr | Delivery of Anti-miRNA-221 for Colorectal Carcinoma Therapy Using Modified Cord Blood Mesenchymal Stem Cells-Derived Exosomes |
title_full_unstemmed | Delivery of Anti-miRNA-221 for Colorectal Carcinoma Therapy Using Modified Cord Blood Mesenchymal Stem Cells-Derived Exosomes |
title_short | Delivery of Anti-miRNA-221 for Colorectal Carcinoma Therapy Using Modified Cord Blood Mesenchymal Stem Cells-Derived Exosomes |
title_sort | delivery of anti-mirna-221 for colorectal carcinoma therapy using modified cord blood mesenchymal stem cells-derived exosomes |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488275/ https://www.ncbi.nlm.nih.gov/pubmed/34616773 http://dx.doi.org/10.3389/fmolb.2021.743013 |
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