Ultrasound-induced Cavitation Research Articles

Degradation of Procion Golden Yellow H-R Dye Using Ultrasound Combined with Advanced Oxidation Process

The current study aims to degrade Procion Golden Yellow H-R through ultrasound-induced cavitation coupled with various oxidants. A comprehensive investigation was conducted to examine the impact of parameters, specifically pH, power, and frequency, on the extent of degradation. The primary aim was to optimize degradation by solely utilizing a cavitation reactor where only 23.8% degradation was observed under the established optimum conditions of pH 2.5, frequency of 22 kHz, and power of 200 W. The investigation of the combined process of cavitation with H2O2, Fenton reagent (H2O2/Fe2+), NaOCl, and potassium persulphate (KPS) was subsequently conducted under optimized conditions. The combined operations greatly enhanced degradation with the use of H2O2 loading of 0.1 g/L leading to 53.3% degradation and the H2O2/Fe2+ ratio of 1:0.25 resulting in 94.6% degradation, while the NaOCl quantum of 0.075 g/L yielded 90% degradation and the KPS quantity of 2 g/L resulted in 97.5% degradation in the specific combinations. A toxicity test on two bacterial strains, Staphylococcus aureus and Escherichia coli, was carried out using the original dye solution and after treatment. The various individual and combination processes were compared using the parameters of cavitational yield and total treatment cost. The study elucidates that combining ultrasonic cavitation with KPS is an effective method for treating wastewater containing Procion Golden Yellow H-R dye, especially when implemented at a larger scale of operation.

Study on high-efficiency sulfide removement using sulfate radical-based AOPs and its oxidation mechanism of refractory gold ore

Pyrite enclosure poses a significant challenge in refractory gold ore processing, inhibiting gold leaching. This study explores Sulfate Radical-based Advanced Oxidation Processes (SR-AOPs) as an effective alternative for pretreating such ores. The oxidation pretreatments were performed under heat and ultrasound activation methods, including heat and ultrasound, and the influences of pretreatment time, pH, ultrasound power, pretreatment temperature, and precursor (PDS) concentration were investigated. Both ultrasonic and heat activation effectively mitigate the negative impact of pyrite enclosure on gold leaching. Specifically, the gold leaching rate improved from 21.9 % to 46.1 % and 74.9 % with heat and ultrasound activation, respectively The and generated by PDS dominate the pyrite oxidation according to EPR and quenching tests. Meanwhile, the SR-AOPs treatment also promotes the interactions between pyrite enclosure and leaching agent, reducing the negative influences of pyrite. Kinetic studies indicated that the oxidation processes are different under heat and ultrasound activation. Heat activation is governed by an interfacial chemical reaction, with an activation energy of 25.57 kJ/mol. In contrast, ultrasound-induced cavitation and microjets remove the oxidation layer, disrupt the pyrite crystal structure, and expose encapsulated gold. These effects accelerate pyrite oxidation, shifting the kinetic control step from interfacial chemical reaction to internal diffusion, with a reduced activation energy of 35.06 kJ/mol.

Investigating the impact of ultrasound on the structural, physicochemical, and emulsifying characteristics of Dioscorin: Insights from experimental data and molecular dynamics simulation

This study investigated the impact of ultrasound treatment on dioscorin, the primary storage protein found in yam tubers. Three key factors, namely ultrasound power, duration, and frequency, were focused on. The research revealed that ultrasound-induced cavitation effects disrupted non-covalent bonds, resulting in a reduction in α-helix and β-sheet contents, decreased thermal stability, and a decrease in the apparent hydrodynamic diameter (Dh) of dioscorin. Additionally, previously hidden amino acid groups within the molecule became exposed on its surface, resulting in increased surface hydrophobicity (Ho) and zeta-potential. Under specific ultrasound conditions (200 W, 25 kHz, 30 min), Dh decreased while Ho increased, facilitating the adsorption of dioscorin molecules onto the oil-water interface. Molecular dynamics (MD) simulations showed that at lower frequencies and pressures, the structural flexibility of dioscorin's main chain atoms increased, leading to more significant fluctuations between amino acid residues. This transformation improved dioscorin's emulsifying properties and its oil-water interface affinity.

Study on the ultrasonic cavitation damage to early atherosclerotic plaque

Ultrasonic cavitation can damage surrounding material and be used for destruction of the target tissue. In this paper, we investigated the interaction between atherosclerotic plaque (AP) and cavitation bubbles to determine whether the mechanical effect of cavitation damage could be potentially useful in therapy for treating atherosclerotic plaques. A two-bubble–fluid–solid model was established to study the dynamic behavior of bubbles near the AP and the AP damage by ultrasound-induced cavitation. A low-intensity focused ultrasound (LIFU) transducer was used for testing cavitation-based AP damage. We found that the nonlinear oscillation of bubbles causes the relative positions of the bubbles to shift, either toward or away from one another, these phenomena lead to changes in the bond failure rate between the fiber bundles, and the value of BRF exhibits an upward trend, this is the reason why the fibers suffered from reversible stretching and compressing. However, the AP damage is irreversible and diminishes as the number of cycles in the ultrasonic burst. It appears that the bigger the radii, regardless of whether the bubble (3 − i)’s and bubble i's radii are equal, the greater the AP damage. Ultrasonic cavitation therapy may not be appropriate for advanced AP patients, and the calcified tissue has a greater impact on the stability of the plaque. The damage area should be strictly selected. Additionally, the tissue damage phenomenon was found in experimental results. This work shows that the severity of AP damage is correlated with acoustic parameters and the surrounding environment from both simulation and experimental perspectives. The results show that ultrasonic cavitation may provide a new choice for the treatment of AP.

Truly Tiny Acoustic Biomolecules for Ultrasound Imaging and Therapy.

Nanotechnology offers significant advantages for medical imaging and therapy, including enhanced contrast and precision targeting. However, integrating these benefits into ultrasonography is challenging due to the size and stability constraints of conventional bubble-based agents. Here bicones, truly tiny acoustic contrast agents based on gas vesicles (GVs), a unique class of air-filled protein nanostructures naturally produced in buoyant microbes, are described. It is shown that these sub-80nm particles can be effectively detected both in vitro and in vivo, infiltrate tumors via leaky vasculature, deliver potent mechanical effects through ultrasound-induced inertial cavitation, and are easily engineered for molecular targeting, prolonged circulation time, and payload conjugation.

Feasibility of in vitro calcification plaque disruption using ultrasound-induced microbubble inertial cavitation

Percutaneous transluminal coronary angioplasty (PTCA) is a clinical method in which plaque-narrowed arteries are widened by inflating an intravascular balloon catheter. However, PTCA remains challenging to apply in calcified plaques since the high pressure required for achieving a therapeutic outcome can result in balloon rupture, vessel rupture, and intimal dissection. To address the problem with PTCA, we hypothesized that a calcified plaque can be disrupted by microbubbles (MBs) inertial cavitation induced by ultrasound (US). This study proposed a columnar US transducer with a novel design to generate inertial cavitation at the lesion site. Experiments were carried out using tubular calcification phantom to mimic calcified plaques. After different parameters of US + MBs treatment (four types of MBs concentration, five types of cycle number, and three types of insonication duration; n = 4 in each group), inflation experiments were performed to examine the efficacy of cavitation for a clinically used balloon catheter. Finally, micro-CT was used to investigate changes in the internal structure of the tubular plaster phantoms. The inflation threshold of the untreated tubular plaster phantoms was > 11 atm, and this was significantly reduced to 7.4 ± 0.7 atm (p = 5.2E-08) using US-induced MBs inertial cavitation at a treatment duration of 20 min with an acoustic pressure of 214 kPa, an MBs concentration of 4.0 × 108 MBs/mL, a cycle number of 100 cycles, and a pulse repetition frequency of 100 Hz. Moreover, micro-CT revealed internal damage in the tubular calcification phantom, demonstrating that US-induced MBs inertial cavitation can effectively disrupt calcified plaques and reduce the inflation threshold of PTCA. The ex vivo histopathology results showed that the endothelium of pig blood vessels remained intact after the treatment. In summary, the results show that US-induced MBs inertial cavitation can markedly reduce the inflation threshold in PTCA without damaging blood vessel endothelia, indicating the potential of the proposed treatment method.

Future perspectives in green hydrogen production by catalyzed sono-photolysis of water

Ultrasound-induced cavitation and dispersed photocatalysts synergistically decompose water into hydrogen, offering higher efficiency. Reasons and future research avenues are explored.

Ultrasound-Induced Microbubble Cavitation for Targeted Delivery of MiR-29b Mimic to Treat Cardiac Fibrosis.

Cardiac fibrosis contributes to adverse ventricular remodeling and is associated with loss of miR-29b. Overexpression of miR-29b via plasmid or intravenous injection of microRNA mimic has blunted fibrosis, but these are inefficient and non-targeted delivery strategies. In this study, we tested the hypothesis that delivery of microRNA-29b (miR-29b) using ultrasound-targeted microbubble cavitation (UTMC) of miR-29b-loaded microbubbles would attenuate cardiac fibrosis and preserve left ventricular (LV) function. Lipid microbubbles were loaded with miR-29b mimic (miR-29b-MB) or negative control (NC) mimic (NC-MB), placed with cardiac fibroblasts (CFs) and treated with pulsed ultrasound. Cells were harvested to measure downstream fibrotic mediators. Mice received angiotensin II (ANG II) infusion causing afterload increase and direct ANG II-induced cardiac fibrosis. UTMC of miRNA-loaded microbubbles was administered to the heart at days 0, 3 and 7. Serial echocardiography was performed, and hearts were harvested on day 10. UTMC treatment of CFs with miR-29b-MB increased miR-29b and decreased fibrotic transcripts compared with NC-MB treatment. In vivo UTMC+NC-MB led to increased LV mass, reduction in cardiac function and increase in fibrotic markers, demonstrating ANGI II-induced adverse cardiac remodeling. Mice treated with UTMC+miR-29b-MB had preservation of cardiac function, downregulation of cardiac fibrillin and trends of lower COL1A1, COL1A2 and COL3 mRNA and decreased cardiac α-smooth muscle protein. UTMC-mediated delivery of miR-29b mimic blunts expression of fibrosis markers and preserves LV function in ANG II-induced cardiac fibrosis.

Degradation of Procion Brilliant Purple H-3R using ultrasound coupled with advanced oxidation processes

The complexity of wastewater matrix poses a challenge for conventional processes especially due to the presence of refractory compounds such as dyes. The present work focuses on utilizing ultrasound-induced cavitation in conjunction with different oxidants such as hydrogen peroxide, Fenton's reagent and potassium persulfate to treat Procion Brilliant Purple H-3R dye containing wastewater. The impact of various operating parameters as pH, frequency, and power on degradation levels has been studied with the aim of optimizing degradation. The optimal conditions for the degradation of Procion Brilliant Purple H-3R were determined as pH of 12, frequency of 22 kHz, and power of 250 W, resulting in a maximum degradation of 70.25%. Combination of a cavitation reactor with hydrogen peroxide, Fenton reagent, and KPS was then applied at optimized conditions, which confirmed a notable enhancement in degradation compared to the only ultrasound based process. Specifically, the degradation extent was 95.99% for combination with H2O2 at 0.5 g/L loading, 99.79% for combination with Fenton at H2O2/Fe2+ ratio of 50:1, and 99.05% for combination with KPS at loading of 0.75 g/L. The kinetic rate constant for the combined approach of US + Fenton was also maximum at 7.47 × 10−1 L mg−1 min−1. Toxicity analysis was conducted on two bacterial strains, Escherichia coli and Staphylococcus aureus, using the wastewater in native form and after treatment. The various processes were evaluated in terms of the cavitational yield and overall treatment cost and it was determined that US + Fenton process is the most efficient treatment method for fully degrading Procion Brilliant Purple H-3R, particularly at larger scales of operation and cost efficiently as demonstrated in the work.

Preparation of Ni–B composite coating doped with hydrothermally modified synthetic WC@MoS2 powders via ultrasonic-assisted jet electrodeposition for corrosion protection

This work aims to improve nanoparticle agglomeration, which hinders the application of nanoparticles in enhancing coating properties. Superhydrophobic and corrosion-resistant Ni–B– MoS2@WC composite coatings were prepared with the help of a simple and inexpensive combination of hydrothermal and electrodeposition techniques. Hydrothermal treatment at 180°C for 24h greatly reduced the specific surface area and improved the hydrophobicity of WC@MoS2 powder. The WC@MoS2 powder showed good dispersion stability in the electrolyte solution. Ni–B/WC@MoS2 composite coatings were prepared through codeposition with metallic Ni2+ under the action of ultrasonic waves. WC@MoS2 powder doping induced the coatings to exhibit a selective orientation of the (111) crystal plane. Ultrasound-induced cavitation increased the participation of nanopowders in the adsorption codeposition of Ni ions. After WC@MoS2 powder doping, the surface roughness of the prepared composite coatings furthered significantly, facilitating the wettability transition. This work investigated the relationship between the surface wettability of the coatings prepared via jet electrodeposition and WC@MoS2 powder doping under auxiliary ultrasonic power. In addition, the effect of surface hydrophobicity on corrosion resistance was examined through electrochemical corrosion tests. The enhanced corrosion resistance of the composite coatings benefits from their enhanced surface roughness and superhydrophobicity. This research offers a proven strategy for improving nanopowders' wettability and composite coatings' corrosion resistance.

Investigation of spatio-temporal inertial cavitation activity for optimization of needle-free ultrasound-enhanced vaccine delivery

Ultrasound-induced cavitation is a promising mechanism for pain-free delivery of vaccines without needles. However, the relationships between cavitation energy and the various bioeffects involved in transdermal vaccination, including skin permeabilization, convective drug transport, reversible and irreversible sonoporation, and immune-stimulation, are not well understood. Previous transdermal ultrasound experiments have demonstrated inhomogeneous delivery across the exposed surface, which remains poorly understood. In this work, we first seek to fully characterize and quantify spatio-temporal cavitation activity across the skin surface, to identify a local cavitation dose that is optimal for all four key bioeffects. We have designed a new in vitro experimental setup that exposes several potential skin models to 265 kHz focused ultrasound, a new generation of protein-based cavitation nuclei (pCaNs), and a fluorescently labelled vaccine analogue, while simultaneously imaging cavitation activity parallel to the skin surface by Passive Acoustic Mapping (PAM). Subsequent staining and multi-photon microscopy of the skin models allows a direct comparison between the PAM-derived spatiotemporal inertial cavitation dose and locations where particular bioeffects were maximized. We will discuss the results of this investigation, how they relate to our recent in vivo study, and whether these findings enable enhancements of the spatial homogeneity and reproducibility of needle-free ultrasound vaccination.

Impact of ultrasonic inertial cavitation on the pancreatic tumor stiffness in mice

Pancreatic ductal adenocarcinoma (PDAC) is among the fastest-growing cancers and is predicted to become the second leading cause of cancer-related deaths worldwide by 2030. Ultrasound-induced inertial cavitation (IC) is an emerging therapeutic strategy with promise for treating patients with unresectable tumors. However, the physical impact of IC on tumors remains unclear. In this study, we used orthotopic murine models of pancreatic cancer and employed passive elastography to measure elasticity before and after applying IC to the whole tumor volume. The IC was generated using two focused confocal transducers (center frequency, 1.1 MHz). The output level was adjusted with a real-time feedback loop based on broadband signal acquired with a passive cavitation detector. Cavitation clouds were visualized during treatment using an imaging probe. The results from eight treated mice showed a 24% decrease (p < 0.05) in tumor stiffness after the IC treatment, indicating that the chosen IC sequence can soften the tumor environment. After sacrifice, we utilized second-harmonic imaging microscopy to visualize the collagen network within the tumor, a known contributor to tissue stiffness, and correlated various features of this network (length, width, curvature) with the measured elasticity.

Nanosecond laser grooving of water-immersed silicon carbide assisted by high intensity focused ultrasound (HIFU)

Silicon carbide (SiC) is a very important semiconductor and ceramic material with many applications. However, its micromachining is difficult and it is still challenging to achieve a good combination of high quality, productivity and low cost. The corresponding author previously proposed the “ultrasound-assisted water-confined laser micromachining” (UWLM) process, a new machining technology utilizing in-situ ultrasound to improve laser machining of a water-covered workpiece. The author's previous studies show that UWLM based upon a high intensity focused ultrasound (HIFU) transducer is able to produce a relatively high machining rate and quality for metals. Thus, it is natural to guess the HIFU-based UWLM process might also possibly help provide a good solution for SiC micromachining. However, SiC have properties very different from metals. An experimental study is critically needed to confirm whether or not HIFU-based UWLM can still produce a high machining rate and quality for SiC, and overcome additional challenge(s) arising (if any). However, such a study is seldom reported to the authors' knowledge. This paper reports a study on the micro grooving of SiC via the HIFU-based UWLM process. With the conditions in this study, it has been found that UWLM can produce a much better apparent groove quality (i.e., much less recast material and/or debris re-deposition) than the laser machining process in the ambient air, and a much higher machining depth per pulse than the laser machining process in water with no ultrasound. The likely fundamental mechanism is the in-situ cleaning effect due to ultrasound-induced cavitation flow and pressure waves in water. The laser machining process in water with or without ultrasound can produce cracks at relatively low pulse repetition rates (PRRs). Time-resolved pressure measurements in water have been performed to help analyze stress sources causing the cracks. The crack problem appears to be effectively solved by using a relatively high PRR of 5 kHz. One possible major reason is expected to be the inter-pulse thermal accumulation effect at the high PRR, improving workpiece fracture toughness and/or reducing temperature gradients.

Prototype of a Coupling Device to Investigate Focused Ultrasound-Induced Inertial Cavitation for Drug Delivery Applications

Abstract Focused ultrasound (FUS) can be used as a drug delivery application for localized chemotherapy to treat cancer. The effect of ultrasound-induced inertial cavitation is promising to trigger drug release from nanocarriers. To investigate this effect, usually, a passive cavitation detection setup is employed. However, applying such a setup is challenging for in vivo experiments, as the test object may need to be fixed inside the water tank. Thus, we present a prototype of a coupling device that could significantly simplify experiments. Since this setup favors undesired sound wave interference and their resulting exceedance of the Mechanical Index, we additionally investigated different signal lengths. The occurrence of standing waves at a signal length of 44 cycles can both be derived from a changing cavitation activity and our calculations. The appearing interference also results in a mean increase of the cavitation activity by ≈ 5.1 %, verified by our experiments as well.

Experimental study on damage mechanism of blood vessel by cavitation bubbles

Ultrasound-induced cavitation in blood vessels is a common scenario in medical procedures. This paper focuses on understanding the mechanism of microscopic damage to vessel walls caused by the evolution of cavitation bubbles within the vessels. In this study, cavitation bubbles were generated using the low-voltage discharge method in 0.9% sodium chloride saline, and vessel models with wall thicknesses ranging from 0.7 mm to 2 mm were made using a 3D laminating process. The interaction between cavitation bubbles and vessel models with different wall thicknesses was observed using a combination of high-speed photography. Results show that cavitation bubble morphology and collapse time increased and then stabilized as the vessel wall thickness increased. When the cavitation bubble was located in vessel axial line, pair of opposing micro-jets were formed along the axis of the vessel, and the peak of micro-jet velocity decreased with increasing wall thickness. However, when the cavitation bubble deviated from the vessel model center, no micro-jet towards the vessel model wall was observed. Further analysis of the vessel wall deformation under varying distances from the cavitation bubble to the vessel wall revealed that the magnitude of vessel wall stretch due to the cavitation bubble expansion was greater than that of the contraction. A comparative analysis of the interaction of between the cavitation bubble and different forms of elastic membranes showed that the oscillation period of the cavitation bubble under the influence of elastic vessel model was lower than the elastic membrane. Furthermore, the degree of deformation of elastic vessel models under the expansion of the cavitation bubble was smaller than that of elastic membranes, whereas the degree of deformation of elastic vessel models in the contraction phase of the cavitation bubble was larger than that of elastic membranes. These new findings provide important theoretical insights into the microscopic mechanisms of blood vessel potential damage caused by ultrasound-induced cavitation bubble, as well as cavitation in pipelines in hydrodynamic systems.

A novel method for the remediation of wastewater containing acid red 131 dye using acoustic cavitation combined with sulphur-doped TiO2 and oxidants.

The present study investigated the degradation of Acid Red 131 (AR131) dye using a combination of ultrasound-induced cavitation, ultraviolet (UV) irradiation, chemical oxidants, and photocatalyst, focusing on the effect of operating parameters. It was established that acidic pH, higher input power, and lower initial concentration resulted in higher degradation. Sulphur-doped titanium dioxide (S-TiO2) synthesized using a novel ultrasound-assisted method showed an optimum dosage of 300ppm for the AR131 degradation with sulphur to titanium ratio of 2:1. In the combination approach, the optimum dosage of hydrogen peroxide (H2O2) and potassium persulfate (KPS) was established as 100ppm and 400ppm respectively. The maximum degradation of 90.3% was obtained using a combined approach of US + KPS + UV/S-TiO2 whereas, a maximum synergetic coefficient of 1.57 was obtained for the approach of US + UV/S-TiO2 with degradation of 86.96%. It was also elucidated that for combination approaches of US + H2O2, US + H2O2 + KPS, and US + H2O2 + KPS + UV/S-TiO2, the synergetic coefficients were lower than one due to undesirable side reactions and radical scavenging. Scale-up studies performed at 15 times of the laboratory scale volume, elucidated that the maximum degradation was obtained as 58.01% for the approach of US + KPS + UV/S-TiO2. Therefore, the approach of US + KPS + UV/S-TiO2 was elucidated as the most efficient in degrading the AR131 dye at both small and large scale of operation. In terms of synergy, the approach of US + UV/S-TiO2 was more efficient. Overall, an optimized combination approach was successfully demonstrated for the effective degradation of AR131 dye with synergism and better results at a large scale.

Portable Handheld "SkinPen" Loaded with Biomaterial Ink for In Situ Wound Healing.

In situ bioprinting has emerged as an attractive tool for directly depositing therapy ink at the defective area to adapt to the irregular wound shape. However, traditional bioprinting exhibits an obvious limitation in terms of an unsatisfactory bioadhesive effect. Here, a portable handheld bioprinter loaded with biomaterial ink is designed and named "SkinPen". Gelatin methacrylate (GelMA) and Cu-containing bioactive glass nanoparticles (Cu-BGn) serve as the main components to form the hydrogel ink, which displays excellent biocompatibility and antibacterial and angiogenic properties. More importantly, by introducing ultrasound and ultraviolet in a sequential programmed manner, the SkinPen achieves in situ instant gelation and amplified (more than threefold) bioadhesive shear strength. It is suggested that ultrasound-induced cavitation and the resulting topological entanglement contribute to the enhanced bioadhesive performance together. Combining the ultrasound-enhanced bioadhesion with the curative role of the hydrogel, the SkinPen shows a satisfactory wound-healing effect in diabetic rats. Given the detachable property of the SkinPen, the whole device can be put in a first-aid kit. Therefore, the application scenarios can be expanded to many kinds of accidents. Overall, this work presents a portable handheld SkinPen that might provide a facile but effective approach for clinical wound management.

A Simple and Cost-Effective Benchtop Setup for Assessing Ultrasound-Induced Inertial Cavitation Probability

Passive cavitation detection methods for measuring ultrasound cavitation events have been utilized for many years. They allow clinicians and researchers to measure cavitation device performance and monitor treatment in real-time. Many methods involve complex processing algorithms and/or expensive measurement hardware. Here we describe and provide open-source resources for a simple benchtop apparatus for measuring the acoustic emissions produced by cavitation events, especially in the context of histotripsy device characterization.

Improved Therapeutic Delivery Targeting Clinically Relevant Orthotopic Human Pancreatic Tumors Engrafted in Immunocompromised Pigs Using Ultrasound-Induced Cavitation: A Pilot Study.

Pancreatic tumors can be resistant to drug penetration due to high interstitial fluid pressure, dense stroma, and disarrayed vasculature. Ultrasound-induced cavitation is an emerging technology that may overcome many of these limitations. Low-intensity ultrasound, coupled with co-administered cavitation nuclei consisting of gas-stabilizing sub-micron scale SonoTran Particles, is effective at increasing therapeutic antibody delivery to xenograft flank tumors in mouse models. Here, we sought to evaluate the effectiveness of this approach in situ using a large animal model that mimics human pancreatic cancer patients. Immunocompromised pigs were surgically engrafted with human Panc-1 pancreatic ductal adenocarcinoma (PDAC) tumors in targeted regions of the pancreas. These tumors were found to recapitulate many features of human PDAC tumors. Animals were intravenously injected with the common cancer therapeutics Cetuximab, gemcitabine, and paclitaxel, followed by infusion with SonoTran Particles. Select tumors in each animal were targeted with focused ultrasound to induce cavitation. Cavitation increased the intra-tumor concentrations of Cetuximab, gemcitabine, and paclitaxel by 477%, 148%, and 193%, respectively, compared to tumors that were not targeted with ultrasound in the same animals. Together, these data show that ultrasound-mediated cavitation, when delivered in combination with gas-entrapping particles, improves therapeutic delivery in pancreatic tumors under clinically relevant conditions.

Ultrasound-induced cavitation renders prostate cancer cells susceptible to hyperthermia: Analysis of potential cellular and molecular mechanisms.

Background: Focused ultrasound (FUS) has become an important non-invasive therapy for prostate tumor ablation via thermal effects in the clinic. The cavitation effect induced by FUS is applied for histotripsy, support drug delivery, and the induction of blood vessel destruction for cancer therapy. Numerous studies report that cavitation-induced sonoporation could provoke multiple anti-proliferative effects on cancer cells. Therefore, cavitation alone or in combination with thermal treatment is of great interest but research in this field is inadequate. Methods: Human prostate cancer cells (LNCap and PC-3) were exposed to 40s cavitation using a FUS system, followed by water bath hyperthermia (HT). The clonogenic assay, WST-1 assay, and Transwell® invasion assay, respectively, were used to assess cancer cell clonogenic survival, metabolic activity, and invasion potential. Fluorescence microscopy using propidium iodide (PI) as a probe of cell membrane integrity was used to identify sonoporation. The H2A.X assay and Nicoletti test were conducted in the mechanism investigation to detect DNA double-strand breaks (DSBs) and cell cycle arrest. Immunofluorescence microscopy and flow cytometry were performed to determine the distribution and expression of 5α-reductase (SRD5A). Results: Short FUS shots with cavitation (FUS-Cav) in combination with HT resulted in, respectively, a 2.2, 2.3, and 2.8-fold decrease (LNCap) and a 2.0, 1.5, and 1.6-fold decrease (PC-3) in the clonogenic survival, cell invasiveness and metabolic activity of prostate cancer cells when compared to HT alone. FUS-Cav immediately induced sonoporation in 61.7% of LNCap cells, and the combination treatment led to a 1.4 (LNCap) and 1.6-fold (PC-3) increase in the number of DSBs compared to HT alone. Meanwhile, the combination therapy resulted in 26.68% of LNCap and 31.70% of PC-3 with cell cycle arrest in the Sub-G1 phase and 35.37% of PC-3 with cell cycle arrest in the G2/M phase. Additionally, the treatment of FUS-Cav combined with HT block the androgen receptor (AR) signal pathway by reducing the relative Type I 5α-reductase (SRD5A1) level to 38.28 ± 3.76% in LNCap cells, and decreasing the relative Type III 5α-reductase 3 (SRD5A3) level to 22.87 ± 4.88% in PC-3 cells, in contrast, the relative SRD5A level in untreated groups was set to 100%. Conclusion: FUS-induced cavitation increases the effects of HT by interrupting cancer cell membranes, inducing the DSBs and cell cycle arrest, and blocking the AR signal pathway of the prostate cancer cells, with the potential to be a promising adjuvant therapy in prostate cancer treatment.