Gas-generating nanoparticles for molecular ultrasound imaging

Abstract

Diagnostic ultrasound imaging often relies on contrast agents. Most common contrast agents are microbubbles that are confined to vascular compartments and molecular targets because micrometer size particles cannot escape through endothelial barriers. Therefore, a desired ultrasound contrast agent should consist of nanometer scale particles that are capable of escaping from vasculature, penetrating into tissue, and then generating sufficient contrast once they reach the target site. We developed a novel contrast agent—plasmonic nanoparticles covered by azide compounds (AzNPs), capable of on-demand laser-induced gas generation via photolysis of azide functional groups. The 50 nm diameter AzNPs were small enough to penetrate the endothelial barrier. Upon laser activation, the AzNPs generated nitrogen gas which served as ultrasound contrast agent. The feasibility of the AzNPs to produce ultrasound contrast was tested within polyethylene tube under laminar flow. Upon laser irradiation, significant ultrasound signal enhancement was observed due to the N2 gas bubbles generated by the photolysis of AzNPs. These and other studies suggest that the AzNPs may enable the ultrasound diagnosis of various diseases that conventional microbubbles cannot detect. Furthermore, these optically absorbing particles can also be used for imaging and therapeutic applications of light and sound such as ultrasound-guided photoacoustic imaging.