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Concept: Sonoporation


Acoustic cavitation plays an important role in sonochemical processes and the rate of sonochemical reaction is influenced by sonication parameters. There are several methods to evaluate cavitation activity such as chemical dosimetry. In this study, to comparison between iodide dosimetry and terephthalic acid dosimetry, efficacy of sonication parameters in reactive radical production has been considered by iodide and terephthalic acid dosimetries. For this purpose, efficacy of different exposure parameters on cavitations production by 1 MHz ultrasound has been studied. The absorbance of KI dosimeter was measured by spectrophotometer and the fluorescence of terephthalic acid dosimeter was measured using spectrofluorometer after sonication. The result of experiments related to sonication time and intensity showed that with increasing time of sonication or intensity, the absorbance is increased. It has been shown that the absorbance for continuous mode is remarkably higher than for pulsing mode (p-value < 0.05). Also results show that with increasing the duty cycles of pulsed field, the inertial cavitation activity is increased. With compensation of sonication time or intensity in different duty cycles, no significant absorbance difference were observed unless 20% duty cycle. A significant correlation between the absorbance and fluorescence intensities (count) at different intensity (R = 0.971), different sonication time (R = 0.999) and different duty cycle (R = 0.967) were observed (p-value < 0.05). It is concluded that the sonication parameters having important influences on reactive radical production. These results suggest that there is a correlation between iodide dosimetry and terephthalic acid dosimetry to examine the acoustic cavitation activity in ultrasound field.

Concepts: Spectroscopy, Light, Ultrasound, Hertz, Sound, Sonochemistry, Cavitation, Sonoporation


Nonviral gene therapy using gemini surfactants is a unique approach to medicine that can be adapted toward the treatment of various diseases. Recently, gemini surfactants have been utilized as candidates for the formation of nonviral vectors. The chemical structure of the surfactant (variations in the alkyl tail length and spacer/head group) and the resulting physicochemical properties of the lipoplexes are critical parameters for efficient gene transfection. Moreover, studying the interaction of the surfactant with DNA can help in designing an efficient vector and understanding how transfection complexes overcome various cellular barriers. Part I of this review provides an overview of various types of gemini surfactants designed for gene therapy and their transfection efficiency; and Part II will focus on different novel methods utilized to understand the interactions between the gemini and DNA in a lipoplex.

Concepts: Medicine, Gene, Genetics, Cell, Molecular biology, Virus, Design, Sonoporation


In the aim of limiting the destructive effects of collapsing bubbles, the regime of stable cavitation activity is currently targeted for sensitive therapeutic applications such as blood-brain barrier opening by ultrasound. This activity is quantified through the emergence of the subharmonic component of the fundamental frequency. Due to the intrinsically stochastic behavior of the cavitation phenomenon, a better control of the different (stable or inertial) cavitation regimes is a key requirement in the understanding of the mechanisms involving each bubble-induced mechanical effect. Current strategies applied to stable cavitation control rely on the use of either seeded microbubbles or a long-lasting pulse to reinitiate subharmonic emission. The present work aims at developing an ultrafast (inferior to 250 μs) monitoring and control of subharmonic emissions during long-pulsed (50 ms) sonication. The use of a FPGA-based feedback loop provides reproducible level of subharmonic emissions combined with temporal stability during the sonication duration. In addition, stable cavitation events are differentiated from the broadband noise characterizing inertial cavitation activity, with perspectives in the discrimination of the involved mechanisms underlying bubble-mediated therapeutic applications.

Concepts: Fluid dynamics, Acoustics, Ultrasound, Control theory, Feedback, Control system, Cavitation, Sonoporation


The exposure of the skin to low-frequency (20-100 kHz) ultrasound is a well-established method for increasing its permeability to drugs. The mechanism underlying this permeability increase has been found to be inertial cavitation within the coupling fluid. This study investigated the influence of acoustic reflections on the inertial cavitation dose during low-frequency (20 kHz) exposure in an in vitro skin sonoporation setup. This investigation was conducted using a passive cavitation detector that monitored the broadband noise emission within a modified Franz diffusion cell. Two versions of this diffusion cell were employed. One version had acoustic conditions that were similar to those of a standard Franz diffusion cell surrounded by air, whereas the second was designed to greatly reduce the acoustic reflection by submerging the diffusion cell in a water bath. The temperature of the coupling fluid in both setups was controlled using a novel thermoelectric cooling system. At an ultrasound intensity of 13.6 W/cm2, the median inertial cavitation dose when the acoustic reflections were suppressed, was found to be only about 15% lower than when reflections were not suppressed.

Concepts: Acoustics, Ultrasound, Sound, Sonar, Sonoluminescence, Cavitation, Sonoporation, Thermoelectric cooling


Gene therapy is an expanding field and it can treat genetic and acquired diseases. It was found that formulations with DNA: CM-β-CD (Carboxymethyl-beta-cyclodextrin): Pluronic-F127 1:3:3 and 1:3 DNA: CM-β-CD are the most stable formulations indicating high incorporation of DNA within CM-β -CD. Gel electrophoresis revealed DNA with low CM-β -CD concentration has formed a more stable complex. Samples 1:3 DNA: CM-β-CD and 1:3:3 DNA: CM-β-CD: Pluronic-127 show no DNA fragment suggesting good condensation of DNA inside cyclodextrin cavity. This was confirmed by fluorescence data where fluorescence intensity was reduced for samples DNA: CM-β-CD 1:3. Overall the findings showed that Carboxymethyl-beta-cyclodextrin (as a novel non-viral gene vector) was able to provide condensation and protection to the DNA, with and without Pluronic-F127, at low concentration. pDNA/CM-β-CD complex has not just shown to be able to transfect COS 7 and SH-SY5Y cell lines but it gave a higher transfection efficiency than that produced by the TransIT-LT1 commercial transfection reagent.

Concepts: Protein, Gene, Genetics, Cell, Molecular biology, Gel electrophoresis, Transfection, Sonoporation


The aim of this study was to evaluate the impact of duration (10, 20 and 30min) and power (100 and 300W) of high-intensity ultrasound (20kHz) on physicochemical properties of beef myofibrillar proteins in order to investigate novel process for modification of its functional characteristics. Results showed that augmentation of duration and power of ultrasound led to enhance pH. Also, the water holding capacity and gel strength were improved by increasing pH. The highest value in pH, reactive sulfhydryl content, water holding capacity and gel strength was obtained in sample subjected to 30min of ultrasound at 300W. The particle size distribution of the proteins was decreased after ultrasound treatment because of the cavitation force of ultrasound waves. In this circumstance, an improvement of emulsifying properties can be obtained. Ultrasonic waves had significant effects on the rheological properties of myofibrillar proteins. Treated samples were more elastic and stiffer than control, although the inverse trend was observed after 30min treatment at each power. Finally, a reducing trend in viscosity was observed by increasing time and power of sonication. Ultrasonic treatment could successfully improve functional properties with effect on physicochemical properties of myofibrillar proteins.

Concepts: Better, Improve, Blood, Ultrasound, Physical chemistry, Particle size distribution, Logarithm, Sonoporation


Ultrasound-driven microbubbles can trigger reversible membrane perforation (sonoporation), open interendothelial junctions and stimulate endocytosis, thereby providing a temporary and reversible time-window for the delivery of macromolecules across biological membranes and endothelial barriers. This time-window is related not only to cavitation events, but also to biological regulatory mechanisms. Mechanistic understanding of the interaction between cavitation events and cells and tissues, as well as the subsequent cellular and molecular responses will lead to new design strategies with improved efficacy and minimized side effects. Recent important progress on the spatiotemporal characteristics of sonoporation, cavitation-induced interendothelial gap and endocytosis, and the spatiotemporal bioeffects and the preliminary biological mechanisms in cavitation-enhanced permeability, has been made. On the basis of the summary of this research progress, this Review outlines the underlying bioeffects and the related biological regulatory mechanisms involved in cavitation-enhanced permeability; provides a critical commentary on the future tasks and directions in this field, including developing a standardized methodology to reveal mechanism-based bioeffects in depth, and designing biology-based treatment strategies to improve efficacy and safety. Such mechanistic understanding the bioeffects that contribute to cavitation-enhanced delivery will accelerate the translation of this approach to the clinic.

Concepts: Improve, Molecular biology, Cell membrane, Molecule, Macromolecule, Membrane, The Delivery, Sonoporation


The way in which a cavitation zone develops in a focused pulsed ultrasound field is studied in this work. Sonoluminescence (SL), total hydrophone output and cavitation noise spectra have been recorded across a gradual, smooth increase in applied voltage. It is shown that the cavitation zone passes through a number of stages of evolution, according to increasing ultrasound intensity, decreasing pulse period and increasing ultrasound pulse duration. Sonoluminescence is absent in the first phase and the hydrophone output spectra consists of a main line with two or three harmonics whose intensity is much lower than that of the main (fundamental) line. The second stage sees the onset of SL whose intensity increases smoothly and is accompanied by the appearance of higher harmonics and subharmonics in the cavitation noise spectra. In some cases, the wide-band (WBN) component can be seen in noise spectra during the final part of the second stage. In the third stage, SL intensity increases significantly and often quite sharply, while WBN intensity increases in the same manner. This is accompanied by a synchronous increase in the absorption of ultrasound by the cavitation zone, which is manifested in a sharp decrease in the hydrophone output. In the fourth stage, both SL and WBN intensities tend to decrease despite the increased voltage applied to the transducer. Furthermore, the fundamental line tends to decrease in strength as well, despite the increasing ultrasound intensity. The obtained results clearly identify the different stages of cavitation zone development using cavitation noise spectra analyses. We then hypothesize that three of the above stages may be responsible for three known types of ultrasound action on biological cells: damping viability, reversible cell damage (sonoporation) and irreversible damage/cytotoxicity.

Concepts: Scientific method, Light, Acoustics, Ultrasound, Sound, Sonar, Sonoluminescence, Sonoporation


This manuscript describes the original structuring of Mg materials under ultrasound irradiation in mild conditions. Golf ball like extended structures can be prepared in dilute oxalic solutions at 20°C under high frequency ultrasound (200kHz). An original approach carried out through iterative 3D reconstruction of sonicated surfaces is used to describe surface evolutions and characterize the formed microstructures. A combination of SEM, ICP-AES, contact-angle measurements, and 3D image analyses allows to characterize the roughness and mass loss evolutions, and investigate the mechanism of formation for such architectures. A screening of the sonication experiments clearly points out an ultrasound frequency dependency for the effects generated at the surface. 200kHz sonication in 0.01M oxalic acid provides an unprecedented manufacturing of Mg samples which result from a controlled and localized dissolution of the material and characterized by a strong wetting surface with a roughness of 170nm. The additional formation of newly formed secondary phases appearing with surface dissolution progress is also deciphered. More generally, the ultrasonic procedure used to prepare these engineered surfaces opens new alternatives for the nano- and micro-structuring of metallic materials which may exhibit advanced physical and chemical properties of potential interest for a large community.

Concepts: Chemistry, Acoustics, Ultrasound, Materials science, Sound, Sonar, Sonoporation, Golf


The microbubble is a kind of clinically applied ultrasound contrast agent in disease diagnosis that can also rupture under sonication to increase membrane permeability and promote gene entry into targeted cells. However, the development of ultrasound-mediated gene delivery might be restricted because genes and microbubbles were separated and would not reach the targeted cells simultaneously. Herein, a kind of crosslinked positive microbubbles (CPMBs) were prepared to load DNA as gene vectors to promote gene delivery efficiency. The BSA shell of the CPMBs was crosslinked with disulfide bonds, which obviously enhanced the stability of the CPMBs. Furthermore, the CPMBs revealed sonoporation effects comparable to those of clinically applied SonoVue microbubbles. As DNA and CPMBs were electrostatically linked as an entirety, they would reach cells simultaneously. Thus, with the aid of ultrasound, these DNA-loaded microbubbles promoted DNA entry into cytoplasm more effectively and obtained higher cellular uptake efficiency and better transfection efficiency than DNA-mixed microbubbles. Confocal microscopy results showed that rupturing of the CPMBs/DNA entire microbubbles under sonication could carry DNA directly into the cytoplasm or nucleus. All results indicated that the cytocompatible DNA-loaded microbubbles have promising prospects in ultrasound-mediated gene delivery.

Concepts: DNA, Protein, Gene, Cell nucleus, Cell, Chromosome, Serum albumin, Sonoporation