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, Kwang Meyung Kim, Ick Chan Kwon, Soo Young Park, Sehoon Kim

Research output: Contribution to journalArticle

Abstract

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
Volume31
Issue number8
DOIs
Publication statusPublished - 2019 Apr 23

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Molecular imaging
Ultrasonics
Gases
Contrast Media
Carbon Monoxide
Imaging techniques
Polyethyleneimine
Chemiluminescence
Polyamines
Colloids
NanoGel
Biocompatibility
Amines
Toxicity
Animals
Nanoparticles
Degradation

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)
  • Materials Chemistry

Cite this

Rational Design of Inflammation-Responsive Inflatable Nanogels for Ultrasound Molecular Imaging. / Heo, Jeongyun; Lim, Chang Keun; Min, Hyun Su; Lee, Kyung Eun; Jeong, Keunsoo; Seo, Young Hun; Lee, Yong Deok; Yhee, Ji Young; Kim, Kwang Meyung; Kwon, Ick Chan; Park, Soo Young; Kim, Sehoon.

In: Chemistry of Materials, Vol. 31, No. 8, 23.04.2019, p. 2905-2912.

Research output: Contribution to journalArticle

Heo, J, Lim, CK, Min, HS, Lee, KE, Jeong, K, Seo, YH, Lee, YD, Yhee, JY, Kim, KM, Kwon, IC, Park, SY & Kim, S 2019, 'Rational Design of Inflammation-Responsive Inflatable Nanogels for Ultrasound Molecular Imaging', Chemistry of Materials, vol. 31, no. 8, pp. 2905-2912. https://doi.org/10.1021/acs.chemmater.9b00167
Heo, Jeongyun ; Lim, Chang Keun ; Min, Hyun Su ; Lee, Kyung Eun ; Jeong, Keunsoo ; Seo, Young Hun ; Lee, Yong Deok ; Yhee, Ji Young ; Kim, Kwang Meyung ; Kwon, Ick Chan ; Park, Soo Young ; Kim, Sehoon. / Rational Design of Inflammation-Responsive Inflatable Nanogels for Ultrasound Molecular Imaging. In: Chemistry of Materials. 2019 ; Vol. 31, No. 8. pp. 2905-2912.
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