Kill two birds with one stone: Engineered exosome-mediated delivery of cholesterol modified YY1-siRNA enhances chemoradiotherapy sensitivity of glioblastoma
Glioblastoma (GBM) is the most malignant tumor of the central nervous system in adults. Irradiation (IR) and temozolomide (TMZ) play an extremely important role in the treatment of GBM. However, major impediments to effective treatment are postoperative tumor recurrence and acquired resistance to ch...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.975291/full |
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| author | Xiao Liu Xiao Liu Zhengcong Cao Nannan Liu Guangxun Gao Mingrui Du Yingwen Wang Boyang Cheng Maorong Zhu Bo Jia Luxiang Pan Wangqian Zhang Yuran Jiang Wei He Linlin Xu Wei Zhang Qunxing An Qingdong Guo Jintao Gu |
| author_facet | Xiao Liu Xiao Liu Zhengcong Cao Nannan Liu Guangxun Gao Mingrui Du Yingwen Wang Boyang Cheng Maorong Zhu Bo Jia Luxiang Pan Wangqian Zhang Yuran Jiang Wei He Linlin Xu Wei Zhang Qunxing An Qingdong Guo Jintao Gu |
| author_sort | Xiao Liu |
| collection | DOAJ |
| description | Glioblastoma (GBM) is the most malignant tumor of the central nervous system in adults. Irradiation (IR) and temozolomide (TMZ) play an extremely important role in the treatment of GBM. However, major impediments to effective treatment are postoperative tumor recurrence and acquired resistance to chemoradiotherapy. Our previous studies confirm that Yin Yang 1 (YY1) is highly expressed in GBM, whereby it is associated with cell dedifferentiation, survival, and therapeutic resistance. Targeted delivery of small interfering RNA (siRNA) without blood-brain barrier (BBB) restriction for eradication of GBM represents a promising approach for therapeutic interventions. In this study, we utilize the engineering technology to generate T7 peptide-decorated exosome (T7-exo). T7 is a peptide specifically binding to the transferrin receptor. T7-exo shows excellent packaging and protection of cholesterol-modified Cy3-siYY1 while quickly releasing payloads in a cytoplasmic reductive environment. The engineered exosomes T7-siYY1-exo could deliver more effciently to GBM cells both in vitro and in vivo. Notably, in vitro experiments demonstrate that T7-siYY1-exo can enhance chemoradiotherapy sensitivity and reverse therapeutic resistance. Moreover, T7-siYY1-exo and TMZ/IR exert synergistic anti-GBM effect and significantly improves the survival time of GBM bearing mice. Our findings indicate that T7-siYY1-exo may be a potential approach to reverse the chemoradiotherapy resistance in GBM. |
| first_indexed | 2024-04-13T18:35:10Z |
| format | Article |
| id | doaj.art-6f3a01cb4d864a1f889903824c326015 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T18:35:10Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-6f3a01cb4d864a1f889903824c3260152022-12-22T02:34:55ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-08-011310.3389/fphar.2022.975291975291Kill two birds with one stone: Engineered exosome-mediated delivery of cholesterol modified YY1-siRNA enhances chemoradiotherapy sensitivity of glioblastomaXiao Liu0Xiao Liu1Zhengcong Cao2Nannan Liu3Guangxun Gao4Mingrui Du5Yingwen Wang6Boyang Cheng7Maorong Zhu8Bo Jia9Luxiang Pan10Wangqian Zhang11Yuran Jiang12Wei He13Linlin Xu14Wei Zhang15Qunxing An16Qingdong Guo17Jintao Gu18State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi’an, ChinaThe First Affiliated Hospital, The Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi’an, ChinaExperimental Teaching Center of Basic Medicine, The Fourth Military Medical University, Xi’an, ChinaThe First Affiliated Hospital, The Fourth Military Medical University, Xi’an, ChinaThe Second Affiliated Hospital, The Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi’an, ChinaThe First Affiliated Hospital, The Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi’an, ChinaThe Third Affiliated Hospital, The Forth Military Medical University, Xi’an, ChinaState Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi’an, ChinaThe First Affiliated Hospital, The Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi’an, ChinaThe First Affiliated Hospital, The Fourth Military Medical University, Xi’an, ChinaThe First Affiliated Hospital, The Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi’an, ChinaGlioblastoma (GBM) is the most malignant tumor of the central nervous system in adults. Irradiation (IR) and temozolomide (TMZ) play an extremely important role in the treatment of GBM. However, major impediments to effective treatment are postoperative tumor recurrence and acquired resistance to chemoradiotherapy. Our previous studies confirm that Yin Yang 1 (YY1) is highly expressed in GBM, whereby it is associated with cell dedifferentiation, survival, and therapeutic resistance. Targeted delivery of small interfering RNA (siRNA) without blood-brain barrier (BBB) restriction for eradication of GBM represents a promising approach for therapeutic interventions. In this study, we utilize the engineering technology to generate T7 peptide-decorated exosome (T7-exo). T7 is a peptide specifically binding to the transferrin receptor. T7-exo shows excellent packaging and protection of cholesterol-modified Cy3-siYY1 while quickly releasing payloads in a cytoplasmic reductive environment. The engineered exosomes T7-siYY1-exo could deliver more effciently to GBM cells both in vitro and in vivo. Notably, in vitro experiments demonstrate that T7-siYY1-exo can enhance chemoradiotherapy sensitivity and reverse therapeutic resistance. Moreover, T7-siYY1-exo and TMZ/IR exert synergistic anti-GBM effect and significantly improves the survival time of GBM bearing mice. Our findings indicate that T7-siYY1-exo may be a potential approach to reverse the chemoradiotherapy resistance in GBM.https://www.frontiersin.org/articles/10.3389/fphar.2022.975291/fullglioblastomaYin Yang 1T7exosomechemoradiotherapy sensitization |
| spellingShingle | Xiao Liu Xiao Liu Zhengcong Cao Nannan Liu Guangxun Gao Mingrui Du Yingwen Wang Boyang Cheng Maorong Zhu Bo Jia Luxiang Pan Wangqian Zhang Yuran Jiang Wei He Linlin Xu Wei Zhang Qunxing An Qingdong Guo Jintao Gu Kill two birds with one stone: Engineered exosome-mediated delivery of cholesterol modified YY1-siRNA enhances chemoradiotherapy sensitivity of glioblastoma Frontiers in Pharmacology glioblastoma Yin Yang 1 T7 exosome chemoradiotherapy sensitization |
| title | Kill two birds with one stone: Engineered exosome-mediated delivery of cholesterol modified YY1-siRNA enhances chemoradiotherapy sensitivity of glioblastoma |
| title_full | Kill two birds with one stone: Engineered exosome-mediated delivery of cholesterol modified YY1-siRNA enhances chemoradiotherapy sensitivity of glioblastoma |
| title_fullStr | Kill two birds with one stone: Engineered exosome-mediated delivery of cholesterol modified YY1-siRNA enhances chemoradiotherapy sensitivity of glioblastoma |
| title_full_unstemmed | Kill two birds with one stone: Engineered exosome-mediated delivery of cholesterol modified YY1-siRNA enhances chemoradiotherapy sensitivity of glioblastoma |
| title_short | Kill two birds with one stone: Engineered exosome-mediated delivery of cholesterol modified YY1-siRNA enhances chemoradiotherapy sensitivity of glioblastoma |
| title_sort | kill two birds with one stone engineered exosome mediated delivery of cholesterol modified yy1 sirna enhances chemoradiotherapy sensitivity of glioblastoma |
| topic | glioblastoma Yin Yang 1 T7 exosome chemoradiotherapy sensitization |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.975291/full |
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