Jacques Lux, UT Southwestern
Late News: Microbubbles Cloaked with Hydrogels as pH-Activatable Ultrasound Contrast Agents
Written by Jessalyn Hui Ying Low
Ultrasound imaging make use of microbubbles (MBs) as contrast agents, and can be used to detect deep vein thrombosis (DVT). However, it is difficult to distinguish acute DVT from chronic DVT, where acute DVT requires aggressive treatment with anticoagulants and can result in internal bleeding. In this talk, Jacques Lux shares how thrombin-specific ultrasound contrast agents can be designed to detect acute DVT through thrombin activity, which is indicative of active thrombosis.
Lux explains that this is achieved by conjugating activatable cell penetrating peptides (ACPPs) to the surface of the MB. In the presence of thrombin, ACPPs will be cleaved causing the MB surface to become positively charged, thus adhering to negatively charged surfaces like fibrin. This allows the microbubbles to be accumulated into clots, exhibiting an increased signal under ultrasound.
To further increase the specificity of these microbubbles to the biomarker of interest (thrombin in this case, but proof of concept done with pH), a hydrogel cloak is added, which contains hyaluronic acid (HA) and a pH-sensitive crosslinker. This serves the purpose of stiffening the MB shell and silencing the harmonic signal in the absence of the biomarker. On the other hand, in the presence of the biomarker, biodegradable crosslinkers in the hydrogel will be cleaved to allow for oscillation of the MB and production of harmonic signal that is specific to the biomarker. It was demonstrated successfully that in acidic pH, harmonic signal was turned on, but not in neutral pH. By extending these hydrogel cloaks to the usage of thrombin-sensitive crosslinkers, these MBs show great potential in exhibiting specificity to thrombin which can be used to detect acute DVT via ultrasound imaging.