A novel peptide-drug conjugate for glioma-targeted drug delivery
Copyright © 2023. Published by Elsevier B.V..
The existence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) greatly limits the application of chemotherapy in glioma. To address this challenge, an optimal drug delivery system must efficiently cross the BBB/BBTB and specifically deliver therapeutic drugs into glioma cells while minimizing systemic toxicity. Here we demonstrated that glucose-regulated protein 78 (GRP78) and dopamine receptor D2 were highly expressed in patient-derived glioma tissues, and dopamine receptors were highly expressed on the BBB. Subsequently, we synthesized a novel "Y"-shaped peptide and compared the effects of different linkers on the receptor affinity and targeting ability of the peptide. A peptide-drug conjugate (pHA-AOHX-VAP-doxorubicin conjugate, pHA-AOHX-VAP-DOX) with a better affinity for glioma cells and higher solubility was derived for glioma treatment. pHA-AOHX-VAP-DOX could cross both BBB and BBTB via dopamine receptor and GRP78 receptor, and finally target glioma cells, significantly prolonging the survival time of nude mice bearing intracranial glioma. Furthermore, pHA-AOHX-VAP-DOX significantly reduced the toxicity of DOX and increased the maximum tolerated dose (MTD). Collectively, this work paves a new avenue for overcoming multiple barriers and effectively delivering chemotherapeutic agents to glioma cells while providing key evidence to identify potential receptors for glioma-targeted drug delivery.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:369 |
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| Enthalten in: |
Journal of controlled release : official journal of the Controlled Release Society - 369(2024) vom: 13. Apr., Seite 722-733 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Jianfen [VerfasserIn] |
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| Links: |
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| Themen: |
Dopamine receptor |
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| Anmerkungen: |
Date Revised 14.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.jconrel.2024.04.011 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370729897 |
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| 520 | |a Copyright © 2023. Published by Elsevier B.V. | ||
| 520 | |a The existence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) greatly limits the application of chemotherapy in glioma. To address this challenge, an optimal drug delivery system must efficiently cross the BBB/BBTB and specifically deliver therapeutic drugs into glioma cells while minimizing systemic toxicity. Here we demonstrated that glucose-regulated protein 78 (GRP78) and dopamine receptor D2 were highly expressed in patient-derived glioma tissues, and dopamine receptors were highly expressed on the BBB. Subsequently, we synthesized a novel "Y"-shaped peptide and compared the effects of different linkers on the receptor affinity and targeting ability of the peptide. A peptide-drug conjugate (pHA-AOHX-VAP-doxorubicin conjugate, pHA-AOHX-VAP-DOX) with a better affinity for glioma cells and higher solubility was derived for glioma treatment. pHA-AOHX-VAP-DOX could cross both BBB and BBTB via dopamine receptor and GRP78 receptor, and finally target glioma cells, significantly prolonging the survival time of nude mice bearing intracranial glioma. Furthermore, pHA-AOHX-VAP-DOX significantly reduced the toxicity of DOX and increased the maximum tolerated dose (MTD). Collectively, this work paves a new avenue for overcoming multiple barriers and effectively delivering chemotherapeutic agents to glioma cells while providing key evidence to identify potential receptors for glioma-targeted drug delivery | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Dopamine receptor | |
| 650 | 4 | |a Doxorubicin | |
| 650 | 4 | |a GRP78 | |
| 650 | 4 | |a Glioma | |
| 650 | 4 | |a Peptide-drug conjugate | |
| 650 | 4 | |a Targeted drug delivery | |
| 700 | 1 | |a Meng, Nana |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Linwei |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Jiasheng |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Sunyi |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Shuai |e verfasserin |4 aut | |
| 700 | 1 | |a Bao, Yanning |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Qianzhu |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ruohan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Cao |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Jinsong |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Weiyue |e verfasserin |4 aut | |
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