Biological Effects Induced by Non-thermal Ultrasound and Implications for Cancer Therapy

Abstract

Recent advancements in imaging and targeting have expanded the utility of ultrasound therapy with increasing attention being paid to the application of ultrasound in cancer therapy.We present in this article a review of the biological effects of non-thermal ultrasound that could find application in cancer treatment in the near and long term. A careful examination of the ultrasound parameters that elicited these observed effects is needed so that one may refine and apply these results for clinical application. Reported biological effects from nonthermal ultrasound have been categorized into mechanical and chemical means of action.Cavitation and acoustic radiation force are the main contributors to sonomechanical effects of ultrasound while reactive oxygen species contribute to its sonochemical effects. These two categories are responsible for observations such as induction of apoptosis in cancer cells, disturbance of the cytoskeleton, enhancement of gene transfection and chemotherapeutic potency, and modulation of cellular proliferation and protein synthesis. In this review we have considered the biological effects of non-thermal ultrasound, the range of parameters at which these biological effects are observed, and the applicability of the observed biological effects to cancer therapy.

Lipid Coated Microbubbles and Low Intensity Pulsed Ultrasound Enhance Chondrogenesis of Human Mesenchymal Stem Cells in 3D Printed Scaffolds

“…Cellular effects of LIPUS are generally categorized to be non-thermal63, predominantly due to cavitation, microstreaming and acoustic radiation forces6465. Cavitation refers to the growth, oscillation, and/or collapse of gaseous cavities under excitation of acoustic waves6667.…”

Promoter hypermethylation as a mechanism for Lamin A/C silencing in a subset of neuroblastoma cells

“…Because silencing of Lamin A/C in neuroblastomas has important mechanical consequences for the cell, low intensity therapeutic ultrasound emerges as a promising therapeutic option for these tumours [97–100]. By studying the overall frequency response of single cell systems to these mechanical stimuli in breast cancer cell lines versus control breast cells(bolstered by finite element method analysis),it has been shown that lower frequencies are needed to ablate cancer cells compared with controls[101].…”

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

“…Although the underlying activity mechanisms of ultrasoundmediated therapies are depended on certain exposure parameters such as intensity, duty factor, ultrasound frequency and pulse repetition frequency, it is well established that non-thermal ultrasound waves may induce the production of ultrasonic cavitation, free radicals, singlet oxygen, reactive oxygen species and ultrasound-mediated apoptosis [12]. Due to the mechanical characteristics of ultrasound waves, changing pressure gradients in liquid leads to the growth, oscillation, and/or collapse of gaseous cavities (bubbles) [13]. Cavitation can be typically observed into two types as stable and inertial, which are regulated by the oscillatory behavior of bubbles under acoustic field [13][14][15][16].…”

“…Due to the mechanical characteristics of ultrasound waves, changing pressure gradients in liquid leads to the growth, oscillation, and/or collapse of gaseous cavities (bubbles) [13]. Cavitation can be typically observed into two types as stable and inertial, which are regulated by the oscillatory behavior of bubbles under acoustic field [13][14][15][16]. Stable cavitation could be identified with the periodic oscillations of gas bubbles that have already existed in the tissue and that could be observed as the waxing bubble during the negative pressure half cycle and the shrinking bubble during the positive pressure half cycle as response to an ultrasound wave field [9,13,17,18].…”

“…Cavitation can be typically observed into two types as stable and inertial, which are regulated by the oscillatory behavior of bubbles under acoustic field [13][14][15][16]. Stable cavitation could be identified with the periodic oscillations of gas bubbles that have already existed in the tissue and that could be observed as the waxing bubble during the negative pressure half cycle and the shrinking bubble during the positive pressure half cycle as response to an ultrasound wave field [9,13,17,18]. Although stable cavitation do not collapse violently at any point of the pressure cycles, inertial cavitation or transient cavitation collapses violently after rapid bubble growth during the negative pressure half cycle and the collapse of cavitation at high-pressure amplitudes leads to instantaneously discharge of highly condensed energy at collapse center that induces localized increase in temperature (104 -106 K) and pressure (81 MPa) in surrounding microenvironment [9,15,19].…”