دورية أكاديمية
Enhanced anti-glioma efficacy of doxorubicin with BRD4 PROTAC degrader using targeted nanoparticles
| العنوان: | Enhanced anti-glioma efficacy of doxorubicin with BRD4 PROTAC degrader using targeted nanoparticles |
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| المؤلفون: | Yihong He, Xin Zan, Junming Miao, Bilan Wang, Yin Wu, Yangmei Shen, Xinchuan Chen, Hongfeng Gou, Songping Zheng, Ning Huang, Yongzhong Cheng, Yan Ju, Xianghui Fu, Zhiyong Qian, Peizhi Zhou, Jiagang Liu, Xiang Gao |
| المصدر: | Materials Today Bio, Vol 16, Iss , Pp 100423- (2022) |
| بيانات النشر: | Elsevier, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Medicine (General) LCC:Biology (General) |
| مصطلحات موضوعية: | Glioma, Resistance, cRGD-PEG-PLA, Doxorubicin, BRD4 PROTAC degrader, Medicine (General), R5-920, Biology (General), QH301-705.5 |
| الوصف: | Current treatment of glioma is hampered due to the physical blood-brain barrier (BBB) and the resistance to traditional chemotherapeutic agents. Herein, we proposed a combined treatment strategy based on Cyclo (Arg-Gly-Asp-d-Phe-Lys) (cRGDfk) peptides-modified nanoparticle named cRGD-P in a self-assembly method for the co-delivery of doxorubicin (DOX) and BRD4 PROTAC degrader ARV-825 (ARV). Molecular dynamics simulations showed that cRGD-P could change its conformation to provide interaction sites for perfectly co-loading DOX and ARV. The cRGD-P/ARV-DOX exhibited an average size of 39.95 nm and a zeta potential of −0.25 mV. Increased expression of BRD4 in glioma cells was observed after being stimulated by cRGD-P/DOX, confirming one of the possible mechanisms of DOX resistance and the synergistic tumor inhibition effect of BRD4 degrading ARV combined with DOX. In the study, the combination of DOX and ARV in the cRGD-P nanoparticle system exhibited synergistic suppression of tumor growth in glioma cells on account of cell cycle arrest in the G2/M phase and the activation of tumor cells apoptosis-related pathways including triggering caspase cascade and downregulating Bcl-2 as well as upregulating Bax. The cRGD-P/ARV-DOX system could effectively suppress the heterotopic and orthotopic growth of glioma by increasing tumor apoptosis, inhibiting tumor proliferation, and decreasing tumor angiogenesis in vivo. Therefore, the cRGD-modified nanoparticle to co-deliver DOX and ARV provides a potential platform for exploiting a more effective and safer combination therapy for glioma. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2590-0064 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2590006422002216; https://doaj.org/toc/2590-0064 |
| DOI: | 10.1016/j.mtbio.2022.100423 |
| URL الوصول: | https://doaj.org/article/288292a33fb2463ba427b6f2b1da8c8c |
| رقم الأكسشن: | edsdoj.288292a33fb2463ba427b6f2b1da8c8c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 25900064 |
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| DOI: | 10.1016/j.mtbio.2022.100423 |