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Engineered exosomes with enhanced stability and delivery efficiency for glioblastoma therapy

Wang, Yutong, Huo, Yiming, Zhao, Chunyuan, Liu, Heng, Shao, Yurou, Zhu, Chenqi, An, Lan, Chen, Xiao, Chen, Zhipeng·2024·Journal of Controlled Release
DOI 10.1016/j.jconrel.2024.02.015
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Abstract

Due to the blood-brain barrier (BBB), the application of chemical drugs for glioblastoma treatment is severely limited. Recently, exosomes have been widely applied for drug delivery to the brain. However, the differences in brain targeting efficiency among exosomes derived from different cell sources, as well as the premature drug leakage during circulation, still limit the therapeutic efficacy. Here, we designed a functional oligopeptide-modified exosome loaded with doxorubicin (Pep2-Exos-DOX) for glioblastoma treatment. BV2 mouse microglial cell line was selected as the exosome source due to the favorable BBB penetration. To avoid drug release in the circulation, a redox-response oligopeptide was designed for incorporation into the membranes of exosomes to lock the drug during circulation. The enrichment of the drug in glioblastoma was confirmed. Pharmacodynamic evaluation showed Pep2-Exos-DOX possessed significant anti-cancer activity against glioblastoma as well as relative biosafety. This exosome-based drug delivery system modified with redox-response oligopeptides provides us a novel strategy for brain diseases treatment.

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Metadata

Authors
Wang, Y., Huo, Y., Zhao, C., Liu, H., Shao, Y., Zhu, C., An, L., Chen, X., & Chen, Z.
Venue
Journal of Controlled Release
Publisher
Elsevier BV
Published
2024-04
Volume
368
Pages
170-183
ISSN
0168-3659
DOI
10.1016/j.jconrel.2024.02.015
Cited by
84
References
7
Language
en
Licence
Funders
National Natural Science Foundation of China

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