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Construction of self-assembled nanogel as mulitenzyme mimics for bioresponsive tandem-catalysis imaging

模拟多酶的自组装纳米凝胶构建及其生物响应性 级联催化诱导成像

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Abstract

The self-assembled phospholipid- or cytosol-associated multienzyme complexes constitute necessary components of the foundation of life. As a proof of concept, metal-coordinated supramolecular nanogels (MCSGs) have been designed, with the self-assembly of di-lysine coordinated iron (Fe(Lys)2)-functionalized peptide gelators on the interface by an in situ amidation-induced protonation process. The monoatomic and highly dispersed active centers of Fe(Lys)2 offered the nanogel mimics with excellent reaction rates due to the high density and nano compartmental structure similar to the natural matrix-associated multienzyme complex. SiO2@MCSGs show both superoxide dismutase (SOD) activity and peroxidase (POD) activity, and the higher activities compared with the activity of free Fe(Lys)2 molecules can be detected. After loading the substrate 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS), SiO2@MCSGsABTS can responsively convert O2− · in the tumor microenvironment into H2O2 intermediates and then tandem catalyzed the oxidization of ABTS for contrast photoacoustic (PA) imaging of tumor by the SOD-POD mimic activity, showing their great potential as the efficient enzymatic agents for pathological theranostics.

摘要

多酶复合物嵌合的自组装基质结构是生命体必要的组成部 分. 受此启发, 本工作基于原位酰胺化反应诱导质子化过程, 在纳米 界面上自组装二赖氨酸配位铁(Fe(Lys)2)功能多肽单元, 设计、构 建了金属配合物基的超分子纳米凝胶(SiO2@MCSGs)材料. 由于其 高度分散的Fe(Lys)2活性中心类似于天然基质相关多酶复合物的 高密度和纳米隔室化结构, 纳米凝胶模拟酶材料显示出优异的催 化效率. SiO2@MCSGs同时呈现出超氧化物歧化酶(SOD)活性和过 氧化物酶(POD)活性, 且与游离Fe(Lys)2分子相比显示超活性性能. 负载底物2,2’-叠氮双-(3-乙基苯并噻唑啉-6-磺酸盐)(ABTS)后, SiO2@MCSGsABTS可以通过SOD模拟酶性能将肿瘤微环境中的 O2 −·迅速转化为H2O2中间体, 然后基于POD模拟活性级联催化氧 化ABTS实现高效的肿瘤光声成像(PA). 具有多酶催化性能的 MCSGs材料显示出对病理区响应性酶催化成像研究的巨大潜力.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (51773155 and 51873156), and the National Key Research and Development Program (2016YFA0100800 and 2018YFC1803100).

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Authors and Affiliations

  1. School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, China

    Xianmeng Xia  (夏贤梦), Xia Wang  (王霞), Xiaoke Han  (韩小珂), Meiyuan Qi  (齐美园), Xingyue He  (何兴月), Kai Pan  (潘开) & Qigang Wang  (王启刚)

  2. Institute of Acoustics, School of Physics Science and Engineering, Tongji University, Shanghai, 200092, China

    Ya Gao  (高雅), Jiangnan Liao  (廖江南) & Qian Cheng  (程茜)

  3. The Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration, Ministry of Education, Tongji University, Shanghai, 200070, China

    Ya Gao  (高雅), Jiangnan Liao  (廖江南) & Qian Cheng  (程茜)

Authors
  1. Xianmeng Xia  (夏贤梦)
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  2. Xia Wang  (王霞)
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  3. Xiaoke Han  (韩小珂)
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  4. Meiyuan Qi  (齐美园)
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  5. Ya Gao  (高雅)
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  6. Jiangnan Liao  (廖江南)
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  7. Xingyue He  (何兴月)
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  8. Kai Pan  (潘开)
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  9. Qian Cheng  (程茜)
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  10. Qigang Wang  (王启刚)
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Contributions

Xia X, Wang X and Wang Q designed the studies and prepared the manuscript. Xia X accomplished most of the experiments including the preparation and characterization of the material, the detection of mimic enzyme activities, the cytotoxicity test and the animal experiments. Cheng Q, Gao Y and Liao J provided support for in vivo photoacoustic detection. Xia X wrote the original draft. Wang X and Wang Q revised the draft elaborately. Qi M, Han X, He X and Pan K made supporting contributions in data curation and formal analysis. All authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Xia Wang  (王霞) or Qigang Wang  (王启刚).

Additional information

Xianmeng Xia is currently studying for a master’s degree in the team of professor Qigang Wang, School of Chemical Science and Engineering, Tongji University. He received a bachelor’s degree from Taiyuan University of Technology. His research interests focus on multifunctional enzymatic hydrogels for tumor imaging and therapy.

Xia Wang is an associate professor at Tongji University, Shanghai, China. Wang received her PhD degree from Shanghai Institute of Ceramics, Chinese Academy of Sciences (CAS) in 2013. Her research interests focus on the multifunctional enzymatic hydrogel composites for biomedical diagnosis and therapy.

Qigang Wang is currently a professor at the School of Chemical Science and Engineering, Tongji University. He received his PhD degree from Shanghai Institute of Ceramics, CAS in 2005. He was the postdoctor of The Hong Kong University of Science and Technology, The University of Tokyo, and Riken from 2005 to 2011. His research interests focus on enzymatic polymerized methodology, printing/molding of fuctional hydrogel or nanogel, and ionic gel electrolyte designs for flexible electronics/bioelectronics.

Conflict of interest

The authors declare no conflict of interest.

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Xia, X., Wang, X., Han, X. et al. Construction of self-assembled nanogel as mulitenzyme mimics for bioresponsive tandem-catalysis imaging. Sci. China Mater. 64, 3079–3086 (2021). https://doi.org/10.1007/s40843-021-1697-x

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  • DOI: https://doi.org/10.1007/s40843-021-1697-x

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