Delivery of siRNA based on engineered exosomes for glioblastoma therapy by targeting STAT3
Small interfering RNA (siRNA) therapy has been considered as a promising strategy for treatment of glioblastoma (GBM), which is an aggressive brain disease with poor prognosis. However, siRNA therapy for GBM is seriously hindered by a multitude of barriers including possible immunogenicity, poor cellular uptake, short blood circulation, poor blood stability and low blood-brain barrier (BBB) penetration. This paper reports Angiopep-2 (An2)-functionalized signal transducers and activators of transcription 3 (STAT3) siRNA-loaded exosomes (Exo-An2-siRNA) as potential therapeutic agents to improve GBM therapy. The experimental results indicate that Exo-An2-siRNA displays high blood stability, efficient cellular uptake, and outstanding BBB penetration ability. Exo-An2-siRNA also exhibits excellent in vitro anti-GBM therapeutic effects due to the exosomes for siRNA protection and An2 modification for GBM targeting and BBB penetration. Such superior properties of Exo-An2-siRNA are responsible for favorable inhibition of the proliferation of orthotopic U87MG xenografts with limited side effects, significantly enhancing the median survival time (MST) of U87MG-bearing nude mice. The developed siRNA therapy featuring An2-functionalized exosomes as nanoplatforms is a safe and effective GBM treatment strategy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Biomaterials science - 10(2022), 6 vom: 15. März, Seite 1582-1590 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liang, Shi-Fu [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 17.03.2022 Date Revised 17.03.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1039/d1bm01723c |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM337114099 |
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| 100 | 1 | |a Liang, Shi-Fu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Delivery of siRNA based on engineered exosomes for glioblastoma therapy by targeting STAT3 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Small interfering RNA (siRNA) therapy has been considered as a promising strategy for treatment of glioblastoma (GBM), which is an aggressive brain disease with poor prognosis. However, siRNA therapy for GBM is seriously hindered by a multitude of barriers including possible immunogenicity, poor cellular uptake, short blood circulation, poor blood stability and low blood-brain barrier (BBB) penetration. This paper reports Angiopep-2 (An2)-functionalized signal transducers and activators of transcription 3 (STAT3) siRNA-loaded exosomes (Exo-An2-siRNA) as potential therapeutic agents to improve GBM therapy. The experimental results indicate that Exo-An2-siRNA displays high blood stability, efficient cellular uptake, and outstanding BBB penetration ability. Exo-An2-siRNA also exhibits excellent in vitro anti-GBM therapeutic effects due to the exosomes for siRNA protection and An2 modification for GBM targeting and BBB penetration. Such superior properties of Exo-An2-siRNA are responsible for favorable inhibition of the proliferation of orthotopic U87MG xenografts with limited side effects, significantly enhancing the median survival time (MST) of U87MG-bearing nude mice. The developed siRNA therapy featuring An2-functionalized exosomes as nanoplatforms is a safe and effective GBM treatment strategy | ||
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| 700 | 1 | |a Ye, Bang-Ce |e verfasserin |4 aut | |
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