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The aim of this study is to investigate how the intracellular ROS responds to different degrees of sonoporation. Using a customized platform for 1.5-MHz ultrasound exposure (13.33-μs duration and 0.70-MPa peak negative pressure) and observing the dynamics of sonoporation and intracellular ROS at the single-cell level, we quantified the exogenous molecular uptake and intracellular ROS indicator to...
Acoustic droplet vaporization (ADV) has shown a great potential in extravascular tumor-targeting theranostics. The mechanical perturbations produced during ADV process (e.g. initial volume expansion, cavitation, and movement of the bubble) on the nearby cells could cause cell dysfunction with irreversible cell membrane damage or facilitate drug delivery due to sonoporation. A confocal acousto-optical...
Medical imaging through a targeting agent promises to improve the specificity and sensitivity of cancer detection. Nanoparticles (NPs) may provide advantages for targeted photoacoustic (PA) imaging due to their unique physical and optical properties. In our previous study, we developed a phase-change contrast agent made from a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA) and loaded...
Invasiveness research is an essential step in breast cancer metastasis. The application of non-contact high frequency ultrasound microbeam stimulation (HFUMS) offers a manner of determining the invasion potential of breast cancer cells. In this article, we compare the calcium elevations elicited in breast cancer cells.
Focused ultrasound enhanced intranasal drug delivery (IN+FUS) is a unique noninvasive approach that utilizes the olfactory pathway to administer drugs directly to the brain. Our group has shown that IN+FUS provides a more homogenous distribution of molecules in the targeted region than intranasal delivery alone. The underlying mechanism of IN+FUS is believed to be due to the microbubble pump effect,...
It is crucial to transport foreign substance into living cells efficiently and minimize adverse side-effects. Using ultrasound microbubble, it is possible to enhance the cellular uptake and transfer the extracellular molecules into cells, this process is called sonoporation. However, the spatial location of microbubbles appears to be a stochastic process, which makes the targeted sonoporation at specific...
Video capsule endoscopy (VCE) is a widely accepted clinical alternative to conventional endoscopy for diagnosis in the gut. Its advantages are that it can visualise the entire gastrointestinal tract including the small bowel (SB) and it is less invasive for the patient. However, VCE is suitable only for diagnosis, with little research into therapeutic capsule endoscopy (TCE). Like VCE, TCE has great...
In this study, a phase-change contrast agent made of biodegradable polymer PLGA and loaded with gold nanorods (GNRs) and perfluorohexane were conjugated to an anti-HER2 antibody (Herceptin) for specific binding to breast cancer cells that overexpress HER2 receptors. The mean size of the nanoparticles (NPs) was about 500 nm. The targeting specificity of PLGA-GNR-Herceptin NPs was examined using fluorescent...
Focused ultrasound with nanodroplets could facilitate localized drug delivery after vaporization with potentially improved in vivo stability, drug payload, and minimal interference outside of the focal zone compared with microbubbles. While the feasibility of blood-brain barrier (BBB) opening using nanodroplets has been previously reported, characterization of the associated delivery has not been...
Giant cluster-like vesicles (GCVs) encapsulating near-infrared fluorescent liposomes and X-ray contrast agents coated with lipids can play a multifunctional role, e.g. preoperatively and intraoperatively localizing tumors and reservoir of a fluorescent tracer for detecting sentinel lymph nodes if they are destroyed. We propose the method to assess the destruction of GCVs using the interaction between...
Systemic chemotherapy has been associated with poor tumor penetration and adverse cytotoxic effects. To combat this, cancer therapy with in-situ forming implants (ISFIs) can provide continuous, high dose release of chemotherapeutic drug directly at the tumor site. However, poor drug distribution through the tumor volume has limited the effectiveness and subsequent translation of ISFIs into clinical...
In situ forming implants (ISFIs) can provide continuous, high dose release of chemotherapeutic drug directly at the tumor site. However, poor drug distribution through the tumor volume has limited the effectiveness and subsequent translation of ISFIs into clinical practice. In this study, mice were subcutaneously injected with phase-inverting ISFIs loaded with fluorescein and exposed to therapeutic...
A high-speed observation system for sonoporation study was improved for observation of bubble and cell dynamics under ultrasound exposure from a lateral direction. The effect of the presence of a scaffold mimicking an in vivo situation on the dynamics was investigated to study the mechanisms by which bubbles cause cell membrane damage. Observations showed that the stiffness of the scaffold has a significant...
Sonophoresis which utilizes ultrasound for transdermal drug delivery (TDD), can increase the skin permeability and improve the efficiency of drug delivery to various drugs. In addition, the addition of microbubbles in sonophoresis accelerate and increase an efficiency of drug delivery. The cavitation induced by sonophoresis with microbubbles on the skin surface may cause disordering of the lipid bilayers...
Invasiveness research is an essential step in breast cancer metastasis. The application of high-frequency ultrasound microbeam stimulation (HFUMS) offers a manner of determining the invasion potential of human breast cancer cells by eliciting the elevation of transient cytoplasmic calcium ions (Ca2+). The fluorescent change in invasive breast cancer cells (MDA-MB-231), reflecting Ca2+ elevation elicited...
Enhancing the cell's membrane permeability enables to promote foreign substance into the cell and has various applications in biomedical engineering. Sonoporation employs the microbubble inertial cavitation to induce reversible cell-pores in the membranes allowing some impermeable molecules to be transferred into cells. However, the inertial cavitation is the violent collapse of bubbles and thus sonoporation...
Type 2 diabetes mellitus is a complex metabolic disease that has reached epidemic proportions. Current pharmacological treatments of this disease include many side effects which can result in complications. We have previously shown that ultrasound is capable of stimulating insulin release from pancreatic beta cells in a safe and effective manner. The aim of this work is to study the role of calcium...
Acoustic droplet vaporization (ADV) has shown a great potential in extravascular tumor-targeting theranostics. During ADV, its mechanical effects on the nearby cells could cause cell dysfunction with irreversible cell membrane damage or facilitate drug delivery by sonoporation. Understanding the real-time characteristics and bio-effects of ADV on cells is significant to develop the approach in vivo...
Localizing tumors and securing resection margins are sometimes difficult especially during laparoscopic surgery for malignant diseases. Therefore, we have developed a tissue marker, which is composed of giant cluster-like vesicles (GCVs) encapsulating near-infrared (NIR) fluorescent liposomes and X-ray contrast agents coated with lipids. The GCVs facilitate localizing tumors preoperatively and intraoperatively...
Multi-modal interface in medicine has been of interest as it extends clinical vision and diagnostic to a higher dimension. In this paper, we develop a real-time intra-operative guidance for robot-assisted surgical operation using a dual photoacoustic (PA) and fluorescence (FL) imaging based on a common pulsed laser and commercial ultrasound array transducer.
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