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

Jeongyun Heo, Chang Keun Lim, Hyun Su Min, Kyung Eun Lee, Keunsoo Jeong, Young Hun Seo, Yong Deok Lee, Ji Young Yhee, Kwangmeyung Kim, Ick Chan Kwon, Soo Young Park, Sehoon Kim

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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 H 2 O 2 -responsive gas (CO 2 )-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 H 2 O 2 -responsive CO 2 -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 nanogel colloid serves as an optimal nanoscale catalytic reactor for the H 2 O 2 -responsive gas generation as well as a gas reservoir capable of nano-to-micro inflation. We demonstrate that the peroxamide-concentrated nanogels are indeed capable of enhancing the ultrasound contrast in response to H 2 O 2 , which allows us to perform diagnostic ultrasound imaging of H 2 O 2 -overproducing inflammatory diseases in mouse models. Along with the biocompatibility of the peroxamide nanogels revealed by the animal toxicity study, our design strategy for the inflatable nanoparticles would contribute to the advancement of activatable contrast agents for ultrasound molecular imaging.

Original languageEnglish
Pages (from-to)2905-2912
Number of pages8
JournalChemistry of Materials
Issue number8
StatePublished - 23 Apr 2019

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© 2019 American Chemical Society.


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