Echographic and physical characterization of albumin-stabilized nanobubbles

Abstract

There has been increasing interest in using nanobubbles (NBs) for ultrasound mediated drug delivery as well as for ultrasound imaging. Albumin NBs are especially attractive for its potential of becoming a versatile platform for drug carriers and molecular targeted therapy agents. However, physical characterization of NBs is generally considered to be difficult due to various technical issues, such as concentration limitations, nanoparticle contamination, etc. In the present study, we measured the size distribution, concentration and weight density of albumin stabilized NBs by means of multiple nanoscale measurement modalities. Laser nanoparticle tracking analysis, multicolor flow cytometry, resonance mass evaluation showed consistent measurement results of the NBs with low mass weight density and diameter size ranging from 100 nm to 400 nm. Furthermore, the NB solution showed excellent images by high frequency ultrasound (30-50 MHz) in flow model acoustic phantoms. The NBs also induced acute cell disruption by low intensity ultrasound (0.8 W/cm 2) irradiation. We successfully fabricated and characterized albumin stabilized NBs which could serve as an effective platform for future theranositic agents.

Influence of Nanobubble Size Distribution on Ultrasound-Mediated Plasmid DNA and Messenger RNA Gene Delivery

“…We showed that the albumin NBs had lower inertial cavitation threshold than lipid shelled NBs in an in vitro cell suspended experiment setup. Results suggested that albumin NBs irradiated with 0.8–1.0 W/cm 2 intensity ultrasound tended to easily collapse and enhanced cancer cell disruption by up to 6.8 fold compared to ultrasound alone ( Watanabe et al, 2019 ). Furthermore, we demonstrated gene transfer into in vitro attached cell culture monolayers and in mice by albumin stabilized NBs in conjunction with a hand-held portable ultrasound imaging device ( Kida et al, 2020 ).…”

“…Human serum albumin-based NBs were prepared according to previous studies reported elsewhere ( Lafond et al, 2018 ; Watanabe et al, 2019 ; Kida et al, 2020 ). Briefly, the air in a plastic container tube (height: 30 mm, outer diameter: 25 mm) was replaced with 15 ml of perfluoropropane gas (C 3 F 8 ; Takachiho Chemical Industrial, Tokyo, JP) using a 23-gauge needle inserted through a small opening in a custom made cap.…”

“…The physical character of NBs was measured as described previously ( Watanabe et al, 2019 ; Kida et al, 2020 ). Briefly, the particle size of NBs was measured by nanoparticle tracking analysis (NTA) device (NanoSight LM10; Malvern Instruments, Worcestershire, United Kingdom).…”

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

“…Acoustic passive cavitation detectors indicated that inertial cavitation threshold was lower than the commercially available MB US contrast agents. Watanabe et al (2019) similarly conducted a detailed study of albumin-based NBs by 3 different nanoscale measurement modalities and characterized the bubble size distribution, gas/particle ratio, and concentration. Subsequently, superior contrast imaging and elevation of time signal intensity curve of the NBs were obtained in an in vitro flow vessel system driven at US frequencies of 40 MHz.…”

“…The physical character of L-NBs and A-NBs were measured as described previously (Watanabe et al, 2019). The particle size of NBs was measured by nanoparticle tracking analysis (NTA) device (NanoSight LM10; Malvern Instruments, Worcestershire, UK).…”