Anticancer effect of hUC-MSC-derived exosome-mediated delivery of PMO-miR-146b-5p in colorectal cancer
© 2023. The Author(s)..
Antisense oligonucleotide (ASO) is a novel therapeutic platform for targeted cancer therapy. Previously, we have demonstrated that miR-146b-5p plays an important role in colorectal cancer progression. However, a safe and effective strategy for delivery of an ASO to its targeted RNA remains as a major hurdle in translational advances. Human umbilical cord mesenchymal cell (hUC-MSC)-derived exosomes were used as vehicles to deliver an anti-miR-146b-5p ASO (PMO-146b). PMO-146b was assembled onto the surface of exosomes (e) through covalent conjugation to an anchor peptide CP05 (P) that recognized an exosomal surface marker, CD63, forming a complex named ePPMO-146b. After ePPMO-146b treatment, cell proliferation, uptake ability, and migration assays were performed, and epithelial-mesenchymal transition progression was evaluated in vitro. A mouse xenograft model was used to determine the antitumor effect and distribution of ePPMO-146b in vivo. ePPMO-146b was taken up by SW620 cells and effectively inhibited cell proliferation and migration. The conjugate also exerted antitumor efficacy in a xenograft mouse model of colon cancer by systematic administration, where PPMO-146b was enriched in tumor tissue. Our study highlights the potential of hUC-MSC-derived exosomes anchored with PPMO-146b as a novel safe and effective approach for PMO backboned ASO delivery.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Drug delivery and translational research - 14(2024), 5 vom: 25. Apr., Seite 1352-1369 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yu, Siming [VerfasserIn] |
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| Links: |
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| Themen: |
Colorectal cancer |
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| Anmerkungen: |
Date Completed 03.04.2024 Date Revised 04.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s13346-023-01469-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364696974 |
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| 520 | |a © 2023. The Author(s). | ||
| 520 | |a Antisense oligonucleotide (ASO) is a novel therapeutic platform for targeted cancer therapy. Previously, we have demonstrated that miR-146b-5p plays an important role in colorectal cancer progression. However, a safe and effective strategy for delivery of an ASO to its targeted RNA remains as a major hurdle in translational advances. Human umbilical cord mesenchymal cell (hUC-MSC)-derived exosomes were used as vehicles to deliver an anti-miR-146b-5p ASO (PMO-146b). PMO-146b was assembled onto the surface of exosomes (e) through covalent conjugation to an anchor peptide CP05 (P) that recognized an exosomal surface marker, CD63, forming a complex named ePPMO-146b. After ePPMO-146b treatment, cell proliferation, uptake ability, and migration assays were performed, and epithelial-mesenchymal transition progression was evaluated in vitro. A mouse xenograft model was used to determine the antitumor effect and distribution of ePPMO-146b in vivo. ePPMO-146b was taken up by SW620 cells and effectively inhibited cell proliferation and migration. The conjugate also exerted antitumor efficacy in a xenograft mouse model of colon cancer by systematic administration, where PPMO-146b was enriched in tumor tissue. Our study highlights the potential of hUC-MSC-derived exosomes anchored with PPMO-146b as a novel safe and effective approach for PMO backboned ASO delivery | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Colorectal cancer | |
| 650 | 4 | |a Drug delivery | |
| 650 | 4 | |a Epithelial-mesenchymal transition | |
| 650 | 4 | |a Exosomes | |
| 650 | 4 | |a hUC-MSCs | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 700 | 1 | |a Liao, Ran |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Lu |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Madi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yumin |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Yushuai |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zhiwei |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Qingwei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Shubin |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Xiaoyi |e verfasserin |4 aut | |
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