Nanobubble Mediated Gene Delivery in Conjunction With a Hand-Held Ultrasound Scanner.

Hiroshi Kida,Koyo Nishimura,Hitomi Endo,Katsuro Tachibana,Akiko Watanabe,Yutaka Irie,Koki Ogawa,Shigeru Kawakami,Loreto B Feril

doi:10.3389/fphar.2020.00363

Hiroshi Kida, Koyo Nishimura + Show 7 more

Open Access

https://doi.org/10.3389/fphar.2020.00363

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Abstract

Recent research has revealed that nanobubbles (NBs) can be an effective tool for gene transfection in conjunction with therapeutic ultrasound (US). However, an approach to apply commercially available hand-held diagnostic US scanners for this purpose has not been evaluated as of now. In the present study, we first compared in vitro, the efficiency of gene transfer (pCMV-Luciferase) with lipid-based and albumin-based NBs irradiated by therapeutic US (1MHz, 5.0 W/cm2) in oral squamous carcinoma cell line HSC-2. Secondly, we similarly examined if gene transfer in mice is possible using a clinical hand-held US scanner (2.3MHz, MI 1.0). Results showed that lipid-based NBs induced more gene transfection compared to albumin-based NBs, in vitro. Furthermore, significant gene transfer was also obtained in mice liver with lipid-based NBs. Sub-micro sized bubbles proved to be a powerful gene transfer reagent in combination with conventional hand-held ultrasonic diagnostic device.

Highlights

For the past two decades, there has been much research on ultrasound (US)-mediated drug delivery
lipid based nanobubbles (L-NBs) were extracted from commercially available US contrast agent, Sonazoid (Daiichi Sankyo, Tokyo, JP), perfluorobutane incapsulated with a phospholipid shell
The size distribution data of the L-NBs and albumin based nanobubbles (A-NBs) obtained from nanoparticle tracking analysis (NTA) is shown in Figures 3A, B

Summary

Introduction

For the past two decades, there has been much research on ultrasound (US)-mediated drug delivery. Recent experiments using high speed video cameras under optic microscopes have shown that oscillation of MBs during US irradiation disrupts the cell membrane to form transient pores (Kudo et al, 2009; Nejad et al, 2016; Song et al, 2019). This phenomenon, frequently referred as sonoporation (Lammertink et al, 2015), induces increase in cell uptake of administrated drugs, molecules, and in some cases plasmid DNA (Sennoga et al, 2017).

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