Research

Research

 

Research Interests

Our research interests lie in the development of novel nanomedicine platforms to diagnose and treat disease in vivo noninvasively.

Our group focuses on two main research topics:

  • Bioresponsive nanomaterials for in vivo detection of disease and therapy
  • Targeted and activatable ultrasound contrast agents

Our long-term objective is to develop clinically translatable theranostic agents.

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

ACS Appl. Mater. Interfaces, 2017, 9 (43), pp 37587–37596

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 increasing concentrations of thrombin lead to cleavage of the FITC-labeled polyanionic chain of the peptide

Results. While there were no significant differences in the signal collected at the end of MB infusion among the three suspensions, (Figure B), there were statistically significant differences in the molecular signal (trapped MBs) between ACPP-MBs and regular MBs (p = 0.0058) and ACPP-MBs with thrombin inhibition using hirudin (p = 0.0012), indicative of thrombin specificity (Figure B). The molecular signal of ACPP-MBs retained after the saline wash indicated that 91.7 ± 14.2% of ACPP-MBs were adherent (Figure C, n=3. * p < 0.05, ** p < 0.01, *** p < 0.001).

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

 

Detecting Pathophysiological Levels of Hydrogen Peroxide with Ultrasound Imaging Using Enzyme-containing Nanoparticles

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.