Therapeutic potential of low-intensity ultrasound (part 2): biomolecular effects, sonotransfection, and sonopermeabilization

Abstract

Part one of this review focused on the thermal and mechanical effects of low-intensity ultrasound (US). In this second and final part of the review, we will focus on and discuss various aspects of low-intensity US, with emphasis on the biomolecular effects, US-mediated gene transfection (sonotransfection), and US-mediated permeabilization (sonopermeabilization). Sonotransfection of different cell lines in vitro and target tissues in vivo have been reported. Optimization experiments have been done and different mechanisms investigated. It has also been found that several genes can be up-regulated or down-regulated by sonication. As to the potential therapeutic applications, systemic or local sonotransfection might also be a safe and effective gene therapy method in effecting the cure of local and systemic disorders. Gene regulation of target cells may be utilized in modifying cellular response to a treatment, such as increasing the sensitivity of diseased cells while making normal cells resistant to the side effects of a treatment. Advances in sonodynamic therapy and drug sonopermeabilization also offer an ever-increasing array of therapeutic options for low-intensity US.

Influence of Low Intensity Ultrasound and Ohmic Heating on Growth of Sake Yeast

“…3B). Therefore, the mechanism may be related to mechanical stimulation of cells or increased uptake of extracellular molecules (Feril et al, 2008) rather than vibration, which increases with increasing ultrasound frequency. Several other studies have demonstrated that the low intensity ultrasound promotes cell proliferation via activation of DNA and protein synthesis (Takeuchi et al, 2008;Saura et al, 2003;Kobayashi et al, 2009).…”

Low-Intensity Continuous Ultrasound Therapies—A Systematic Review of Current State-of-the-Art and Future Perspectives

“…US has multiple biological effects, including thermal, cavitation, microstreaming, nutrient exchange, and oxygenation [ 34 , 35 , 36 , 37 ]. The thermal effects of US are related to ultrasonic parameters and tissue density, with US impedance and attenuation determining the level of heat generated in the tissue and subsequent increases in vasodilation, oxygenation, and nutrient exchange [ 37 ].…”

“…The thermal effects of US are related to ultrasonic parameters and tissue density, with US impedance and attenuation determining the level of heat generated in the tissue and subsequent increases in vasodilation, oxygenation, and nutrient exchange [ 37 ]. Ultrasound’s properties of cavitation and microstreaming are attributed to the continuous cycle of compression and refraction of microbubbles within inertial fluids leading to localized stress and loosening of the matrix and cell membrane, thereby increasing the exchange of nutrients and promoting drug delivery [ 36 ]. Considering the multifactorial effects of US, it is an attractive therapeutic tool to target multiple degenerative, cancerous, and infectious diseases.…”

“…Numerous studies have examined the effectiveness of low-intensity pulsed US (LIPUS) and low-intensity continuous US (LICUS) as potential means of tissue regeneration and treatment for disorders such as pain, thrombosis, fracture healing, osteoporosis, and osteoarthritis [24,[26][27][28][29][30][31][32][33]. US has multiple biological effects, including thermal, cavitation, microstreaming, nutrient exchange, and oxygenation [34][35][36][37]. The thermal effects of US are related to ultrasonic parameters and tissue density, with US impedance and attenuation determining the level of heat generated in the tissue and subsequent increases in vasodilation, oxygenation, and nutrient exchange [37].…”

Ultrasound-Mediated Cancer Therapy as a Noninvasive and Repeatable Treatment Strategy

“…Ultrasound-mediated chemotherapy, sonoporation, drug delivery, gene delivery etc. principally use these sonomechanical effects to disrupt the normal functions of the cellular membranes [21]. The sonochemical effects of the bubble collapse can be monitored as the generation of free radicals, singlet oxygen and reactive oxygen species, and / or the occurring of sonoluminescence that can activate the sonosensitizer molecules [19].…”