Focused shockwave induced blood-brain barrier opening and transfection

• Published in: Scientific reports Vol. 8; no. 1; pp. 2218 - 11
• Main Authors: Kung, Yi, Lan, Chiang, Hsiao, Ming-Yen, Sun, Ming-Kuan, Hsu, Yi-Hua, Huang, Abel P.-H., Liao, Wei-Hao, Liu, Hao-Li, Inserra, Claude, Chen, Wen-Shiang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.02.2018; Nature Publishing Group
• Subjects: 42/109; 59/5; 631/378/1341; 631/61/2300/1851; 639/166/985; Animals; Blood-brain barrier; Blood-Brain Barrier - radiation effects; Brain - radiation effects; Drug delivery; Extracorporeal Shockwave Therapy - methods; Genes, Reporter; Genetic Therapy - methods; High-Energy Shock Waves; Humanities and Social Sciences; Luciferases - analysis; Luciferases - genetics; multidisciplinary; Rats; Rodents; Science; Science (multidisciplinary); Shock waves; Transfection; Ultrasound
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-20672-y

Despite extensive efforts in recent years, the blood-brain barrier (BBB) remains a significant obstacle for drug delivery. This study proposes using a clinical extracorporeal shockwave instrument to open the BBB, combined with a laser assisted bi-axial locating platform to achieve non-invasive, controllable-focus and reversible BBB opening in the brains of rats. Under shockwave treatment with an intensity level of 5 (P – 9.79 MPa, energy flux density (EFD) 0.21 mJ/mm 2 ) and a pulse repetition frequency of 5 Hz, the BBB could be opened after 50 shocks without the use of an ultrasound contrast agent. With the proposed method, the BBB opening can be precisely controlled in terms of depth, size and location. Moreover, a shockwave based gene transfection was demonstrated using a luciferase gene.