Angiogenesis-targeting microbubbles combined with ultrasound-mediated gene therapy in brain tumors
| Autor: | Ching Hsiang Fan, En-Ling Chang, Yuan-Chih Chang, Yu-Chun Lin, En Chi Liao, Chiung Yin Huang, Chi-Shiun Chiang, Hao-Li Liu, Po Hong Hsu, Chih-Kuang Yeh, Hong-Lin Chan, Chien Yu Ting, Kuo Chen Wei |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetic enhancement Brain tumor Pharmaceutical Science Brain damage Gene delivery Biology Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Luciferases Firefly Glioma Gene expression medicine Animals Microbubbles Neovascularization Pathologic Brain Neoplasms Gene targeting DNA Genetic Therapy medicine.disease Vascular Endothelial Growth Factor Receptor-2 Molecular biology 030104 developmental biology Ultrasonic Waves 030220 oncology & carcinogenesis Cancer research medicine.symptom |
| Zdroj: | Journal of Controlled Release. 255:164-175 |
| ISSN: | 0168-3659 |
| Popis: | The major challenges in gene therapy for brain cancer are poor transgene expression due to the blood-brain barrier (BBB) and neurologic damage caused by conventional intracerebral injection. Non-viral gene delivery using ultrasound-targeted microbubbles (MBs) oscillation via the systematic transvascular route is attractive, but there is currently no high-yielding and targeted gene expression method. In this study, we developed a non-viral and angiogenesis-targeting gene delivery approach for efficient brain tumor gene therapy without brain damage. We developed a VEGFR2-targeted and cationic microbubbles (VCMBs) gene vector for use with transcranial focused ultrasound (FUS) exposure to allow transient gene delivery. The system was tested in a brain tumor model using the firefly luciferase gene and herpes simplex virus type 1 thymidine kinase/ganciclovir (pHSV-TK/GCV) with VCMBs under FUS exposure for transgene expression and anti-tumor effect. In vitro data showed that VCMBs have a high DNA-loading efficiency and high affinity for cancer cells. In vivo data confirmed that this technique enhanced gene delivery into tumor tissues without affecting normal brain tissues. The VCMBs group resulted in higher luciferase expression (3.8 fold) relative to the CMBs group (1.9 fold), and the direct injection group. The tumor volume on day 25 was significantly smaller in rats treated with the pHSV-TK/GCV system using VCMBs under FUS (9.7±5.2mm3) than in the direct injection group (40.1±4.3mm3). We demonstrated the successful use of DNA-loaded VCMBs and FUS for non-viral, non-invasive and targeted gene delivery to brain tumors. |
| Databáze: | OpenAIRE |
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