Dual-Enzyme-Loaded Multifunctional Hybrid Nanogel System for Pathological Responsive Ultrasound Imaging and T2-Weighted MRI

Significance Statement

As an emerging material, nanogel system is hydrogel nanoparticle, its ideal fluid-like transport properties and hydrophilic environment make the nanogel a perfect candidate for bio-catalysis, biomedical diagnosis and therapy. The immobilization (encapsulation) of enzymes within the gel matrix provides protection from structural alterations and subsequent deactivation of the enzymes, ensuring higher loadings and better substrate mobility for efficient catalysis. In addition, the unique hydrophilic environment and water-rich structure of this nanogel make it an ideal probe for magnetic resonance (MR) imaging, where the signal detected is directly related to relaxation time.

In this work, focused on exploiting the structure-function relationships of hydrogel, the dual-enzyme loaded multifunctional magnetic nanogel, which is composed of functionalized superparamagnetic iron oxide (SPIO) particles, a dual enzyme species (catalase and superoxide dismutase) and a polysaccharide cationic polymer glycol chitosan gel, was developed to be an efficient and safe probe for dual-modality pathological responsive ultrasound (US) and T₂-weighted MR imaging both in vitro and in vivo.

About the author

Prof. Dr. Hui-Xiong Xu, MD, PhD is the Head and Professor of Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Ultrasound Research and Education Institute, Tongji University School of Medicine (i.e. the First Affiliated Hospital), Shanghai, China. He is an Expert Panel Member of International Guideline of Contrast Enhanced Ultrasound in the Liver by World Federation of Ultrasound in Medicine and Biology (WFUMB), and a Member of International Contrast Ultrasound Society. His research interest includes US-guided ablation for tumor, Contrast-enhanced ultrasound, and US elastography.

About the author

Dr. Qi-Gang Wang received his Ph.D. from Shanghai Institute of Ceramics, Chinese Academy of Sciences in 2005. From 2005 to 2011, he continued his research works in The Hong Kong University of Science and Technology, the University of Tokyo and Riken. He joined Tongji as a full professor and Young’s 1000 plan in 2011. His research interests will focus on 1) the mild radical polymerization for the preparation of nanocomposite gel, 2) the 3D printing and hierarchical pore design of functional gel, 3) the potential applications of functional gel in the interdisciplinary fields. He has published over thirty papers as first author and corresponding author including Nature.

About the author

Dr. Xia Wang is an Assistant Professor of Chemistry department at Tongji University, China. Her research interests focus on the multifunctional nanogel composites and mesoporous silica-based nanomaterials for biomedical diagnosis and therapy.

Journal Reference

ACS Nano. 2015;9(6):5646-56.

Wang X¹, Niu D², Li P³, Wu Q¹, Bo X³, Liu B³, Bao S¹, Su T¹, Xu H³, Wang Q¹.

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Department of Chemistry and Advanced Research Institute, Tongji University, Shanghai, 200092, China.
Lab of Low-Dimensional Materials Chemistry, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, China.
Department of MedicalUltrasound, Shanghai Tenth People’s Hospital, Tenth People’s Hospital of Tongji University, Shanghai, 200072, China.

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Abstract

A dual-enzyme-loaded multifunctional hybrid nanogel probe (SPIO@GCS/acryl/biotin-CAT/SOD-gel, or SGC) has been developed for dual-modality pathological responsive ultrasound (US) imaging and enhanced T2-weighted magnetic resonance (MR) imaging. This probe is composed of functionalized superparamagnetic iron oxide particles, a dual enzyme species (catalase and superoxide dismutase), and a polysaccharide cationic polymer glycol chitosan gel. The dual-modality US/MR imaging capabilities of the hybrid nanogel for responsive US imaging and enhanced T2-weighted MR imaging have been evaluated both in vitro and in vivo. These results show that the hybrid nanogel SGC can exhibit efficient dual-enzyme biocatalysis with pathological species for responsive US imaging. SGC also demonstrates increased accumulation in acidic environments for enhanced T2-weighted MR imaging. Further research on these nanogel systems may lead to the development of more efficient US/MR contrast agents.

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Figure legend: Dual-Enzyme Loaded Hybrid Nanogel System for Pathological Responsive US and MR imaging.