Modulation control over ultrasound-mediated gene delivery: Evaluating the importance of standing waves

• Published in: Journal of controlled release Vol. 141; no. 1; pp. 70 - 76
• Main Authors: Hassan, Mariame A., Buldakov, Mikhail A., Ogawa, Ryohei, Zhao, Qing-Li, Furusawa, Yukihiro, Kudo, Nobuki, Kondo, Takashi, Riesz, Peter
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 04.01.2010
• Subjects: Apoptosis; Cell Culture Techniques; DNA - administration & dosage; DNA - genetics; Equipment Design; Flow Cytometry; Gene delivery; Gene Transfer Techniques; HeLa Cells; Humans; Low-intensity ultrasound; Luciferases - genetics; Phonophoresis - instrumentation; Pulse repetition frequency (PRF); Sonication - instrumentation; Standing waves; Transfection; Ultrasonics; Ultrasound streaming; Standing waves; Gene delivery; Low-intensity ultrasound; Ultrasound streaming; Pulse repetition frequency (PRF)
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2009.08.020

Low modulation frequencies from 0.5 to 100 Hz were shown to alter the characteristics of the ultrasound field producing solution agitation (< 5 Hz; region of “ultrasound streaming” prevalence) or stagnancy (> 5 Hz; region of standing waves establishment) (Buldakov et al., Ultrason. Sonochem., 2009). In this study, the same conditions were used to depict the changes in exogenous DNA delivery in these regions. The luciferase expression data revealed that lower modulations were more capable of enhancing delivery at the expense of viability. On the contrary, the viability was conserved at higher modulations whereas delivery was found to be null. Cavitational activity and acoustic streaming were the effecters beyond the observed pattern and delivery enhancement was shown to be mediated mainly through sonopermeation. To promote transfection, the addition of calcium ions or an echo contrast agent (Levovist ®) was proposed. Depending on the mechanism involved in each approach, differential enhancement was observed in both regions and at the interim zone (5 Hz). In both cases, enhancement in standing waves field was significant reaching 16.0 and 3.3 folds increase, respectively. Therefore, it is concluded that although the establishment of standing waves is not the only prerequisite for high transfection rates, yet, it is a key element in optimization when other factors such as proximity and cavitation are considered. [Display omitted]