Effective Delivery of DNA Octahedron Nanocages Loading Epirubicin by Ultrasound with Microbubbles Improved Therapeutic Effect on Nude Mice Bearing Intracranial Glioblastoma Xenografts

The effect of chemotherapy of glioblastoma was limited due to the formidable obstacle of the blood-brain barrier (BBB). Low-intensity ultrasound combined with microbubbles (US/MB) has been a promising approach to deliver therapeutic agents across the BBB noninvasively and reversibly. DNA nanostructures have been used as drug carriers offering multiple advantages of structural controllability, high loading capacity and low cytotoxicity. Herein, this study constructed DNA octahedron nanocages (DNA-Octa) carrying Epirubicin (Dox@DNA), which were delivered to the brain by US/MB. Cy 5.5-labeled DNA-Octa efficiently accumulated in the brain sonicated by US/MB. Moreover, nude mice bearing intracranial glioblastoma xenografts were established. Compared with Control group, the released Dox concentration in tumor homogenates in the US/MB+Dox@DNA group increased by 5.6 times. US/MB+Dox@DNA significantly retarded the intracranial glioblastoma growth, reduced tumor cell proliferation and increased cell apoptosis. The results suggested that DNA nanomedicines delivered by low-intensity ultrasound with microbubbles may provide a positive and promising therapeutic strategy against glioblastoma.