Exosome Delivered Anticancer Drugs Across the Blood-Brain Barrier for Brain Cancer Therapy in Danio Rerio

By Tianzhi Yang, Paige Martin, B. Fogarty, Alison Brown, Kayla Schurman, R. Phipps, Viravuth P. Yin, P. Lockman, Shuhua Bai. Pharmaceutical Research, 2015

923 citations recorded by the source corpus.

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. 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. 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. Brain endothelial cell derived exosomes could be potentially used as a carrier for brain delivery of anticancer drug for the treatment of brain cancer.

Subfields: Molecular Biology, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/1acfa240977d9d76c9edf9655c02ba4fc5bbcbc4

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In Molecular Biology

1. Ramesh C. Gupta
2. Yan Luo
3. Ben Wang
4. F. Aqil
5. Chuanjiang He
6. Shu Zheng
7. Radha Munagala
8. S. Alahari

Citations in the corpus

• Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications (2020, positive): “Yang et al. 99 used the zebrafish model to examine the efficacy of brain endothelial-derived exosomes to deliver the anti-tumor drug doxorubicin through the blood-brain barrier.”
• Using exosomes, naturally-equipped nanocarriers, for drug delivery (2015, background): “A similar result was reported for HepG2 cells that were incubated with different anticancer agents: PTX, Etoposide, Carboplatin, Irinotecan, Epirubicin, and Mitoxantrone [108].”
• Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance (2019, background): “Exosome-based delivery approach of adriamycin and paclitaxel has been used for targeted cancer therapy and resulted in minimal immunogenicity and toxicity [142, 143].”
• Exosome Theranostics: Biology and Translational Medicine (2018, background): “In addition, other therapeutic compounds, such as paclitaxel [172] and doxorubicin [173], can be packaged into exosomes for crossing the blood-brain barrier and achieving targeted delivery.”
• Bovine milk-derived exosomes for drug delivery (2015, background): “Recent studies have exploited the idea of both passive methods such as incubation [48] and active encapsulation techniques such as electroporation, saponin treatment, extrusion and hypotonic dialysis [49, 50] for drug loading in cell-derived exosomes.”