Effects of Microbubble Size on Ultrasound-Mediated Gene Transfection in Auditory Cells

Abstract

Gene therapy for sensorineural hearing loss has recently been used to insert genes encoding functional proteins to preserve, protect, or even regenerate hair cells in the inner ear. Our previous study demonstrated a microbubble- (MB-)facilitated ultrasound (US) technique for delivering therapeutic medication to the inner ear. The present study investigated whether MB-US techniques help to enhance the efficiency of gene transfection by means of cationic liposomes on HEI-OC1 auditory cells and whether MBs of different sizes affect such efficiency. Our results demonstrated that the size of MBs was proportional to the concentration of albumin or dextrose. At a constant US power density, using 0.66, 1.32, and 2.83 μm albumin-shelled MBs increased the transfection rate as compared to the control by 30.6%, 54.1%, and 84.7%, respectively; likewise, using 1.39, 2.12, and 3.47 μm albumin-dextrose-shelled MBs increased the transfection rates by 15.9%, 34.3%, and 82.7%, respectively. The results indicate that MB-US is an effective technique to facilitate gene transfer on auditory cells in vitro. Such size-dependent MB oscillation behavior in the presence of US plays a role in enhancing gene transfer, and by manipulating the concentration of albumin or dextrose, MBs of different sizes can be produced.

Multiparameter evaluation of in vivo gene delivery using ultrasound-guided, microbubble-enhanced sonoporation

“…Previous studies showed that cavitation behavior and stability of microbubbles mainly depend on microbubble size [43, 44]. The natural frequency of microbubbles depends on their diameter [45].…”

Ultrastructural Changes Associated With the Enhanced Permeability of the Round Window Membrane Mediated by Ultrasound Microbubbles

“…This technique not only increases the permeability of the RWM and facilitates drug delivery into the inner ear, but the preliminary results also show no resulting damage to the integrity of the RWM or deterioration of the hearing thresholds, as assessed by auditory brainstem responses. Furthermore, in 2014, we demonstrated that USMBs were effective at facilitating gene transfer to auditory cells in vitro (Liao et al, 2014) and that the size-dependent MB oscillation behavior in the presence of US plays a role in enhancing gene transfer. In addition, dexamethasone delivery to the round window of animals with the aid of USMBs has a greater efficacy in protecting the inner ear from noise-exposed injury when compared to a simple soaking with the drug (Shih et al, 2019).…”

Targeted Transthoracic Acoustic Activation of Systemically Administered Nanodroplets to Detect Myocardial Perfusion Abnormalities

“…The 600–650 nanometer sized droplets would be expected to result in microbubbles that were at least 3–4 microns in size (7), and perhaps slightly larger due to inward diffusing dissolved nitrogen gas within the blood stream. Even at these sizes though, they would still be expected to pass freely through the myocardial capillaries (13) while also being more resistant to destruction than smaller sized perfluorocarbon microbubbles (14). Intravenously infused commercially available microbubbles within the capillaries would not be visualized at this high mechanical index and frame rate, since capillary blood replenishment with intravenously infused C3 microbubbles would not be expected at this frame speed (10).…”