Rational Design of Inflammation-Responsive Inflatable Nanogels for Ultrasound Molecular Imaging

Microbubbles are clinically used as an imaging agent for contrast-enhanced ultrasound image. Beyond the preformed microbubbles, nanoscale gas-generating chemical systems that are capable of stimulus-responsive inflation to microbubbles have recently been employed as a new echogenic strategy for ultrasound molecular imaging. Here, we report a peroxamide-based ultrasound contrast agent as a H2O2-responsive gas (CO2)-generating system for diagnostic ultrasound imaging of inflammatory diseases. A hydrolytic degradation-resistant peroxamide nanogel was constructed by nanoscopic cross-linking of polymeric aliphatic amines (branched polyethyleneimine) with oxalyl chloride, which intrinsically offers highly concentrated peroxamides as a reactive cross-linking point for H2O2-responsive CO2-generation by the peroxalate chemiluminescence reaction that is intrinsically catalyzed by the polyamine-derived intraparticle basic environment. It was experimentally revealed that the interior of the peroxamide-concentrated na...