دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: Exosome-mediated delivery platform of biomacromolecules into the brain: Cetuximab in combination with doxorubicin for glioblastoma therapy.
المؤلفون: Chu L; 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., Sun Y; 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., Zhao Y; 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., Wang A; 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., Sun Y; Shandong Business Institute, Yantai, 264670, China., Duan X; 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., Li N; 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., Xia H; 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., Liu W; 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., Sun K; 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.
المصدر: International journal of pharmaceutics [Int J Pharm] 2024 Jul 20; Vol. 660, pp. 124262. Date of Electronic Publication: 2024 May 28.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 7804127 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3476 (Electronic) Linking ISSN: 03785173 NLM ISO Abbreviation: Int J Pharm Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.
مواضيع طبية MeSH: Doxorubicin*/administration & dosage , Doxorubicin*/pharmacology , Doxorubicin*/pharmacokinetics , Exosomes*/metabolism , Glioblastoma*/drug therapy , Glioblastoma*/metabolism , Glioblastoma*/pathology , Cetuximab*/administration & dosage , Cetuximab*/pharmacology , Brain Neoplasms*/drug therapy , Brain Neoplasms*/metabolism , Blood-Brain Barrier*/metabolism, Animals ; Humans ; Cell Line, Tumor ; Rats ; Drug Delivery Systems/methods ; Male ; Brain/metabolism ; Rats, Sprague-Dawley ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Rats, Nude
مستخلص: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Blood-brain barrier; Cetuximab; Doxorubicin; Exosomes; Glioblastoma
المشرفين على المادة: 80168379AG (Doxorubicin)
PQX0D8J21J (Cetuximab)
تواريخ الأحداث: Date Created: 20240530 Date Completed: 20240712 Latest Revision: 20240712
رمز التحديث: 20240713
DOI: 10.1016/j.ijpharm.2024.124262
PMID: 38815637
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-3476
DOI:10.1016/j.ijpharm.2024.124262