Targeted Extracellular Vesicles Delivered Verrucarin A to Treat Glioblastoma
| Autor: | Kai Chen, Yingnan Si, Jia-Shiung Guan, Zhuoxin Zhou, Seulhee Kim, Taehyun Kim, Liang Shan, Christopher D. Willey, Lufang Zhou, Xiaoguang Liu |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Biomedicines Biomedicines; Volume 10; Issue 1; Pages: 130 Biomedicines, Vol 10, Iss 130, p 130 (2022) |
| ISSN: | 2227-9059 |
| Popis: | Glioblastomas, accounting for approximately 50% of gliomas, comprise the most aggressive, highly heterogeneous, and malignant brain tumors. The objective of this study was to develop and evaluate a new targeted therapy, i.e., highly potent natural compound verrucarin A (Ver-A), delivered with monoclonal antibody-directed extracellular vesicle (mAb-EV). First, the high surface expression of epidermal growth factor receptor (EGFR) in glioblastoma patient tissue and cell lines was confirmed using immunohistochemistry staining, flow cytometry, and Western blotting. mAb-EV-Ver-A was constructed by packing Ver-A and tagging anti-EGFR mAb to EV generated from HEK293F culture. Confocal microscopy and the In Vivo Imaging System demonstrated that mAb-EV could penetrate the blood–brain barrier, target intracranial glioblastoma xenografts, and deliver drug intracellularly. The in vitro cytotoxicity study showed IC50 values of 2–12 nM of Ver-A. The hematoxylin and eosin staining of major organs in the tolerated dose study indicated minimal systemic toxicity of mAb-EV-Ver-A. Finally, the in vivo anti-tumor efficacy study in intracranial xenograft models demonstrated that EGFR mAb-EV-Ver-A effectively inhibited glioblastoma growth, but the combination with VEGF mAb did not improve the therapeutic efficacy. This study suggested that mAb-EV is an effective drug delivery vehicle and natural Ver-A has great potential to treat glioblastoma. |
| Databáze: | OpenAIRE |
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