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Exosome-mediated delivery platform of biomacromolecules into the brain: Cetuximab in combination with doxorubicin for glioblastoma therapy

Chu, Liuxiang, Sun, Yuchen, Zhao, Yanyan, Wang, Aiping, Sun, Yiying, Duan, Xinliu, Li, Nuannuan, Xia, Hangyu, Liu, Wanhui, Sun, Kaoxiang·2024·International Journal of Pharmaceutics
DOI 10.1016/j.ijpharm.2024.124262
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Abstract

Monoclonal antibodies (mAbs) have become the predominant treatment modality for various diseases due to their high affinity and specificity. Although antibodies also have great potential for neurological diseases, they couldn't fully meet the therapeutic requirements due to their high molecular weight and limitations in crossing the blood-brain barrier (BBB). Herein, an innovative strategy based on exosomes (Exos) platform was developed to enhance the delivery of cetuximab (CTX) into the brain, and in combination with doxorubicin (DOX) for the synergistic targeted therapy of glioblastoma (GBM). The in vitro/vivo experiments have shown that exosomes could effectively promote BBB penetration and increase the content of CTX in glioma cells and brain lesions. Cytotoxicity and wound healing experiments have shown that CTX-Exo-DOX could significantly inhibit the proliferation of tumor cells. Finally, in vivo results showed that CTX-Exo-DOX significantly prolonged the survival time of tumor-bearing rats to 28 days, which was 1.47 times that of the DOX group. In summary, exosomes could deliver more antibodies into the brain, and CTX-Exo-DOX is a promising co-delivery system for the treatment of GBM. The results of this study will also provide a prospective strategy for antibody drugs in the treatment of neurological diseases.

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Metadata

Authors
Chu, L., Sun, Y., Zhao, Y., Wang, A., Sun, Y., Duan, X., Li, N., Xia, H., Liu, W., & Sun, K.
Venue
International Journal of Pharmaceutics
Publisher
Elsevier BV
Published
2024-07
Volume
660
Pages
124262
ISSN
0378-5173
DOI
10.1016/j.ijpharm.2024.124262
Cited by
20
References
5
Language
en
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