2. Academic Validation
  3. Exosome-mediated delivery platform of biomacromolecules into the brain: Cetuximab in combination with doxorubicin for glioblastoma therapy

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

  • Int J Pharm. 2024 May 28:660:124262. doi: 10.1016/j.ijpharm.2024.124262.
Liuxiang Chu 1,  Yuchen Sun 2,  Yanyan Zhao 2,  Aiping Wang 3,  Yiying Sun 4,  Xinliu Duan 2,  Nuannuan Li 2,  Hangyu Xia 2,  Wanhui Liu 2,  Kaoxiang Sun 5
Affiliations

Affiliations

  • 1 Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, School of Pharmacy, Yantai University, Yantai, Shandong 264005, China; Yantai Laishan Fourth People's Hospital, Yantai, 264003, China.
  • 2 Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, School of Pharmacy, Yantai University, Yantai, Shandong 264005, China.
  • 3 Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, School of Pharmacy, Yantai University, Yantai, Shandong 264005, China. Electronic address: wangaipingytu@163.com.
  • 4 Shandong Business Institute, Yantai, 264670, China.
  • 5 Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, School of Pharmacy, Yantai University, Yantai, Shandong 264005, China; National Key Laboratory of Advanced Drug Delivery and Release Systems, Novapath Pharma (Chengdu) Co., Ltd., Chengdu, Sichuan 610200, China. Electronic address: sunkx@ytu.edu.cn.
PMID: 38815637 DOI: 10.1016/j.ijpharm.2024.124262
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.

Keywords

Blood-brain barrier; Cetuximab; Doxorubicin; Exosomes; Glioblastoma.

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