Ultrasound Facilitates Naturally Equipped Exosomes Derived from Macrophages and Blood Serum for Orthotopic Glioma Treatment
| Autor: | Lianmei Bai, Pan Wang, Xiaobing Wang, Quanhong Liu, Kun Zhang, Kaili Guo, Yichen Liu |
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| Rok vydání: | 2019 |
| Předmět: |
Materials science
Ultrasonic Therapy macromolecular substances Blood–brain barrier Exosomes 03 medical and health sciences Mice 0302 clinical medicine Blood serum In vivo Glioma Cell Line Tumor medicine Animals General Materials Science 030304 developmental biology 0303 health sciences Brain Neoplasms Macrophages fungi food and beverages Neoplasms Experimental medicine.disease Microvesicles In vitro carbohydrates (lipids) enzymes and coenzymes (carbohydrates) medicine.anatomical_structure RAW 264.7 Cells Blood-Brain Barrier 030220 oncology & carcinogenesis Drug delivery Cancer research Nanocarriers |
| Zdroj: | ACS applied materialsinterfaces. 11(16) |
| ISSN: | 1944-8252 |
| Popis: | Exosomes (Exos) are endogenous nanocarriers that have utility as novel delivery systems for the treatment of brain cancers. However, in general, natural Exos show limited BBB-crossing capacity and lack specific targeting. Further modifications including targeting peptides and genetic engineering approaches can circumvent these issues, but the process is time-consuming. Focused ultrasound (FUS) has been approved by the Food and Drug Administration for the diagnosis and treatment of brain diseases due to its noninvasive nature, reversibility, and instantaneous local opening of the BBB. In this study, we developed a natural and safe transportation system using FUS to increase the targeted delivery of Exos for glioma therapy. We also compared the advantages of macrophage-derived Exos (R-Exos) and blood serum-derived Exos (B-Exos) to screen for an improved platform with scope for clinical transformation. In vitro, both R-Exos and B-Exos were transported through BBB models and accumulated in glioma cells with the assistance of ultrasound exposure. R-Exos and B-Exos displayed no obvious differences in physical characteristics, drug release, tumor targeting, and cytotoxicity when combined with FUS. In vivo animal imaging studies suggested that the fluorescence intensity of B-Exos plus single FUS in brains was 4.45-fold higher than that of B-Exos alone. Furthermore, B-Exos plus twice FUS treatment efficiently suppressed glioma growth with no obvious side effects. We therefore demonstrate that the combination of FUS and naturally abundant B-Exos is a potent strategy for brain cancer therapeutics. |
| Databáze: | OpenAIRE |
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