Stimulus-activatable echogenic maltodextrin nanoparticles as nanotheranostic agents for peripheral arterial disease.

Abstract

Reactive oxygen species (ROS) are closely related with various pathological disorders. Therefore, real-time detection of ROS is essential for understanding the procedure of diseases and diagnosing the accurate lesion sites. Hydrogen peroxide (H₂O₂) accounts for a large portion of ROS and has a longer half-life than other ROS, which makes it a highly promising diagnostic and therapeutic biomarker. In this work, we developed H₂O₂-activatable CO₂ bubble generating indocyanine green-loaded boronated maltodextrin (ICG-BM) nanoparticles for imaging and therapy of peripheral arterial disease. ICG-BM nanoparticles displayed increasing fluorescence, ultrasound and photoacoustic signals in H₂O₂-triggered manners and exerted significant anti-inflammatory and proangiogenic effects in H₂O₂-stimulated vascular endothelial cells. In mouse models of hindlimb ischemia, ICG-BM nanoparticles also showed H₂O₂-triggered amplification of fluorescence, ultrasound and photoacoustic signals in the ischemic hindlimb muscles. ICG-BM nanoparticles also significantly reduced the level of overproduced H₂O₂ and exerted highly potent anti-inflammatory and proangiogenic activities in the ischemic tissues. We therefore believe that pathological stimulus-activatable echogenic ICG-BM nanoparticles provide a new avenue for imaging and treatment of peripheral arterial disease.