Research

Research

 

Research Interests

Our group is interested in developing new targeted and activatable ultrasound (US) agents that not only aid in cancer detection, but also release drugs and/or destroy tumors with high-intensity focused ultrasound.

Other research interests include the development of nanoprobes for MRI, PET, and CT imaging of cancer.

 

Illustration

Current Projects

Development of thrombin-sensitive activatable US contrast agents for the detection of acute thrombosis

Objective. Acute deep vein thrombosis (DVT) is the formation of a blood clot in the deep veins of the body that can lead to fatal pulmonary embolism. Acute DVT is difficult to distinguish from chronic DVT and is therefore treated aggressively with anticoagulants, which can lead to internal bleeding. We aim to develop a contrast agent that detects acute thrombosis with ultrasound imaging.

Activatable contrast agents are activated in the presence of thrombin and accumulate to enhance the ultrasound signal.

Method. Acute clotting occurs when thrombin is activated. We are using activatable cell-penetrating peptides (ACPP) composed of a  polycationic chain and a fluorescently-labeled (FITC)polyanionic chain that neutralizes the charge. Upon cleavage of the peptide by thrombin, the polyanionic peptide is dissociated yielding the polycationic-labeled reporter that adheres to cell membranes.

Addition of thrombin leads to the cleavage of the peptide and release of the FITC-labeled polyanionic chain 

Development of enzyme-responsive nanoprobes for the detection of inflammatory diseases using ultrasound imaging

Objective. Elevated Hydrogen Peroxide (H2O2) levels (>30µM) in tissues is the hallmark of oxidative stress that is implicated in many diseases including cancer. There is no current method to detect H2O2 in vivo except for optical imaging, which is severely limited by poor penetration. To that end, the goal of this project is to develop an ultrasound-based strategy for in vivo H2O2 detection.

 

Catalase is encapsulated in physically crosslinked nanogels that are subsequently coated with a silica shell.

 

Method. We formulated silica nanoshell particles (NSP) containing catalase, an enzyme that converts H2O2 into O2 and water, and aimed to detect O2 microbubbles with ultrasound. In vitro imaging was done with a Siemens Sequoia 512 (15L8 transducer).

Addition of hydrogen peroxide leads to the generation of oxygen microbubbles that are detected with an ultrasound scanner.