PUBLICATION
Exosome Delivered Anticancer Drugs Across the Blood-Brain Barrier for Brain Cancer Therapy in Danio Rerio
- Authors
- Yang, T., Martin, P., Fogarty, B., Brown, A., Schurman, K., Phipps, R., Yin, V.P., Lockman, P., Bai, S.
- ID
- ZDB-PUB-150123-12
- Date
- 2015
- Source
- Pharmaceutical research 32(6): 2003-14 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Zebrafish
- Technology, Pharmaceutical/methods
- Capillary Permeability
- Cell Line, Tumor
- Drug Delivery Systems/methods*
- Animals
- Time Factors
- Humans
- Disease Models, Animal
- Doxorubicin/chemistry
- Doxorubicin/metabolism
- Doxorubicin/pharmacology*
- Green Fluorescent Proteins/biosynthesis
- Green Fluorescent Proteins/genetics
- Endothelial Cells/metabolism*
- Particle Size
- Exosomes/metabolism*
- Antineoplastic Agents/chemistry
- Antineoplastic Agents/metabolism
- Antineoplastic Agents/pharmacology*
- Neoplasm Transplantation
- Animals, Genetically Modified
- Heterografts
- Endocytosis
- Chemistry, Pharmaceutical
- Brain Neoplasms/drug therapy*
- Brain Neoplasms/genetics
- Brain Neoplasms/metabolism
- Brain Neoplasms/pathology
- Blood-Brain Barrier/metabolism*
- Tumor Burden/drug effects
- Genes, Reporter
- Paclitaxel/chemistry
- Paclitaxel/metabolism
- Paclitaxel/pharmacology*
- Cell Proliferation/drug effects
- PubMed
- 25609010 Full text @ Pharm. Res.
Citation
Yang, T., Martin, P., Fogarty, B., Brown, A., Schurman, K., Phipps, R., Yin, V.P., Lockman, P., Bai, S. (2015) Exosome Delivered Anticancer Drugs Across the Blood-Brain Barrier for Brain Cancer Therapy in Danio Rerio. Pharmaceutical research. 32(6):2003-14.
Abstract
Purpose The blood-brain barrier (BBB) essentially restricts therapeutic drugs from entering into the brain. This study tests the hypothesis that brain endothelial cell derived exosomes can deliver anticancer drug across the BBB for the treatment of brain cancer in a zebrafish (Danio rerio) model.
Materials and methods Four types of exosomes were isolated from brain cell culture media and characterized by particle size, morphology, total protein, and transmembrane protein markers. Transport mechanism, cell uptake, and cytotoxicity of optimized exosome delivery system were tested. Brain distribution of exosome delivered anticancer drugs was evaluated using transgenic zebrafish TG (fli1: GFP) embryos and efficacies of optimized formations were examined in a xenotransplanted zebrafish model of brain cancer model.
Results Four exosomes in 30-100 diameters showed different morphologies and exosomes derived from brain endothelial cells expressed more CD63 tetraspanins transmembrane proteins. Optimized exosomes increased the uptake of fluorescent marker via receptor mediated endocytosis and cytotoxicity of anticancer drugs in cancer cells. Images of the zebrafish showed exosome delivered anticancer drugs crossed the BBB and entered into the brain. In the brain cancer model, exosome delivered anticancer drugs significantly decreased fluorescent intensity of xenotransplanted cancer cells and tumor growth marker.
Conclusions Brain endothelial cell derived exosomes could be potentially used as a carrier for brain delivery of anticancer drug for the treatment of brain cancer.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping