Ultrasound enhanced siRNA delivery using cationic liposome-microbubble complexes for the treatment of squamous cell carcinoma.

Microbubble () contrast agents combined with ultrasound targeted microbubble cavitation () are a promising platform for site-specific therapeutic oligonucleotide delivery. We investigated UTMC-mediated delivery of siRNA directed against epidermal growth factor receptor (), to squamous cell carcinoma () via a novel MB-liposome complex (). were constructed by conjugation of cationic liposomes to the surface of CF gas-filled lipid MBs using biotin/avidin chemistry, then loaded with siRNA via electrostatic interaction.

Fibrin-targeted phase shift microbubbles for the treatment of microvascular obstruction.

Microvascular obstruction (MVO) following percutaneous coronary intervention (PCI) is a common problem associated with adverse clinical outcomes. We are developing a novel treatment, termed sonoreperfusion (SRP), to restore microvascular patency. This entails using ultrasound-targeted microbubble cavitation (UTMC) of intravenously administered gas-filled lipid microbubbles (MBs) to dissolve obstructive microthrombi in the microvasculature.

Non-invasive Assessment of Liver Fat in ob/ob Mice Using Ultrasound-Induced Thermal Strain Imaging and Its Correlation with Hepatic Triglyceride Content.

Non-alcoholic fatty liver disease is the accumulation of triglycerides in liver. In its malignant form, it can proceed to steatohepatitis, fibrosis, cirrhosis, cancer and ultimately liver impairment, leading to liver transplantation. In a previous study, ultrasound-induced thermal strain imaging (US-TSI) was used to distinguish between excised fatty livers from obese mice and non-fatty livers from control mice.

Validation of Ultrasound Super-Resolution Imaging of Vasa Vasorum in Rabbit Atherosclerotic Plaques.

Acute coronary syndromes and strokes are mainly caused by atherosclerotic plaque (AP) rupture. Abnormal increase of vasa vasorum (VV) is reported as a key evidence of plaque progression and vulnerability. However, due to their tiny size, it is still challenging to noninvasively identify VV near the major vessels.

Ultrasound and Microbubble-targeted Delivery of a microRNA Inhibitor to the Heart Suppresses Cardiac Hypertrophy and Preserves Cardiac Function.

MicroRNAs (miRs) are dysregulated in pathological left ventricular hypertrophy. AntimiR inhibition of miR-23a suppressed hypertension-induced cardiac hypertrophy in preclinical models, but clinical translation is limited by a lack of cardiac-targeted delivery systems. Ultrasound-targeted microbubble cavitation (UTMC) utilizes microbubbles as nucleic acid carriers to target delivery of molecular therapeutics to the heart.

Super-resolution ultrasound imaging method for microvasculature in vivo with a high temporal accuracy.

Traditional ultrasound imaging techniques are limited in spatial resolution to visualize angiogenic vasa vasorum that is considered as an important marker for atherosclerotic plaque progression and vulnerability. The recently introduced super-resolution imaging technique based on microbubble center localization has shown potential to achieve unprecedented high spatial resolution beyond the acoustic diffraction limit. However, a major drawback of the current super-resolution imaging approach is low temporal resolution because it requires a large number of imaging frames.

Ultrasound Targeted Microbubble Destruction-Mediated Delivery of a Transcription Factor Decoy Inhibits STAT3 Signaling and Tumor Growth.

Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in many cancers where it acts to promote tumor progression. A STAT3-specific transcription factor decoy has been developed to suppress STAT3 downstream signaling, but a delivery strategy is needed to improve clinical translation. Ultrasound-targeted microbubble destruction (UTMD) has been shown to enhance image-guided local delivery of molecular therapeutics to a target site.

Noninvasive detection of lipids in atherosclerotic plaque using ultrasound thermal strain imaging: in vivo animal study.

Objectives: This study sought to examine the feasibility of in vivo detection of lipids in atherosclerotic plaque (AP) by ultrasound (US) thermal (or temporal) strain imaging (TSI).

Background: Intraplaque lipid content is thought to contribute to plaque stability. Lipid exhibits a distinctive physical characteristic of temperature-dependent US speed compared with water-bearing tissues.

Ultrasound-targeted microbubble destruction to deliver siRNA cancer therapy.

Microbubble contrast agents can specifically deliver nucleic acids to target tissues when exposed to ultrasound treatment parameters that mediate microbubble destruction. In this study, we evaluated whether microbubbles and ultrasound-targeted microbubble destruction (UTMD) could be used to enhance delivery of EGF receptor (EGFR)-directed siRNA to murine squamous cell carcinomas. Custom-designed microbubbles efficiently bound siRNA and mediated RNAse protection.

Modulation of pre-capillary arteriolar pressure with drag-reducing polymers: a novel method for enhancing microvascular perfusion.

Objective: We have shown that drag-reducing polymers (DRP) enhance capillary perfusion during severe coronary stenosis and increase red blood cell velocity in capillaries, through uncertain mechanisms. We hypothesize that DRP decreases pressure loss from the aorta to the arteriolar compartment.

Methods: Intravital microscopy of the rat cremaster muscle and measurement of pressure in arterioles (diameters 20-132 μm) was performed in 24 rats.

Gene therapy of carcinoma using ultrasound-targeted microbubble destruction.

When microbubble contrast agents are loaded with genes and systemically injected, ultrasound-targeted microbubble destruction (UTMD) facilitates focused delivery of genes to target tissues. A mouse model of squamous cell carcinoma was used to test the hypothesis that UTMD would specifically transduce tumor tissue and slow tumor growth when treated with herpes simplex virus thymidine kinase (TK) and ganciclovir. UTMD-mediated delivery of reporter genes resulted in tumor expression of luciferase and green fluorescent protein (GFP) in perivascular areas and individual tumor cells that exceeded expression in control tumors (p=0.

Vascular endoluminal delivery of mesenchymal stem cells using acoustic radiation force.

Restoration of functional endothelium is a requirement for preventing late stent thrombosis. We propose a novel method for targeted delivery of stem cells to a site of arterial injury using ultrasound-generated acoustic radiation force. Mesenchymal stem cells (MSCs) were surface-coated electrostatically with cationic gas-filled lipid microbubbles (mb-MSC).

Quantification of plaque neovascularization using contrast ultrasound: a histologic validation.

Aims: The density of vasa vasorum within atherosclerotic plaque correlates with histologic features of plaque vulnerability in post-mortem studies. Imaging methods to non-invasively detect vasa vasorum are limited. We hypothesized that contrast ultrasound (CUS) can quantify vasa vasorum during atherosclerosis progression.

A novel hydrodynamic method for microvascular flow enhancement.

We have shown that drag-reducing polymers (DRP) restore perfusion to a stenotic bed by lowering microvascular resistance. We studied whether resistance-lowering by DRP are due to changes in hydrodynamics or vasodilation. During intravital microscopy of rat cremaster muscle (n=18), DRP infusion increased aortic flow (p<0.