Ultrasound-responsive nanobubble-mediated gene transfection in the cerebroventricular region by intracerebroventricular administration in mice

Koki Ogawa; Yuki Fuchigami; Masayori Hagimori; Shintaro Fumoto; Kazuo Maruyama; Shigeru Kawakami

doi:10.1016/j.ejpb.2019.02.003

Ultrasound-responsive nanobubble-mediated gene transfection in the cerebroventricular region by intracerebroventricular administration in mice

Eur J Pharm Biopharm. 2019 Apr:137:1-8. doi: 10.1016/j.ejpb.2019.02.003. Epub 2019 Feb 7.

Authors

Koki Ogawa¹, Yuki Fuchigami², Masayori Hagimori³, Shintaro Fumoto⁴, Kazuo Maruyama⁵, Shigeru Kawakami⁶

Affiliations

¹ Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan.
² Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan. Electronic address: y-fuchigami@nagasaki-u.ac.jp.
³ Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan. Electronic address: hagimori@nagasaki-u.ac.jp.
⁴ Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan. Electronic address: sfumoto@nagasaki-u.ac.jp.
⁵ Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashiku, Tokyo 173-8605, Japan. Electronic address: maruyama@pharm.teikyo-u.ac.jp.
⁶ Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan. Electronic address: skawakam@nagasaki-u.ac.jp.

PMID: 30738859
DOI: 10.1016/j.ejpb.2019.02.003

Abstract

Aim: Intracerebroventricular (ICV) administration of ultrasound-responsive bubbles and cranial ultrasound irradiation is reported as a transfection system for the cerebroventricular region. This study aimed to characterize the transfection system with respect to transfection efficiency, spatial distribution of transgene expression, and safety.

Methods: Plasmid DNA was transfected to mouse brain by ICV injection of ultrasound-responsive nanobubbles, followed by ultrasound irradiation to brain. Spatial distribution of transgene expression in the cerebroventricular region was investigated using multicolor deep imaging.

Result: This transfection system efficiently transferred the transgene to the choroid plexus with no morphological change or cerebral hemorrhage. Moreover, sustained secretion of transgenic protein was achieved by transferring the transgene encoding the secretable protein.

Conclusion: We successfully developed an ultrasound-responsive nanobubbles-mediated method for gene transfection into the cerebroventricular region via ICV administration in mice.

Keywords: Choroid plexus; Gene delivery; Intracerebroventricular injection; Nanobubbles; Ultrasound; plasmid DNA.

MeSH terms

Animals
Brain / metabolism
DNA / administration & dosage*
Gene Transfer Techniques
Injections, Intraventricular
Male
Mice
Nanostructures*
Plasmids / administration & dosage
Transfection / methods*
Ultrasonic Waves*

Substances

DNA