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Biomimetic enzyme nanocomplexes and their use as antidotes and preventive measures for alcohol intoxication

Nature Nanotechnology volume 8, pages 187192 (2013) | Download Citation

Abstract

Organisms have sophisticated subcellular compartments containing enzymes that function in tandem. These confined compartments ensure effective chemical transformation and transport of molecules, and the elimination of toxic metabolic wastes1,2. Creating functional enzyme complexes that are confined in a similar way remains challenging. Here we show that two or more enzymes with complementary functions can be assembled and encapsulated within a thin polymer shell to form enzyme nanocomplexes. These nanocomplexes exhibit improved catalytic efficiency and enhanced stability when compared with free enzymes. Furthermore, the co-localized enzymes display complementary functions, whereby toxic intermediates generated by one enzyme can be promptly eliminated by another enzyme. We show that nanocomplexes containing alcohol oxidase and catalase could reduce blood alcohol levels in intoxicated mice, offering an alternative antidote and prophylactic for alcohol intoxication.

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Acknowledgements

This work was partially supported by the Defense Threat Reducing Agency (DTRA), the National Institutes of Health (NIH, grants R01AA018846 and R01AA018612), the National Natural Science Foundation of China (NSFC, grants 81025018, 91127045 and 50830103) and the National Basic Research Program of China (973 Program, no. 2011CB932500).

Author information

Author notes

    • Yang Liu
    •  & Juanjuan Du

    These authors contributed equally to this work

Affiliations

  1. Key Laboratory of Functional Polymer Materials, Ministry of Education, and Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China

    • Yang Liu
    •  & Linqi Shi
  2. Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, California 90095, USA

    • Yang Liu
    • , Juanjuan Du
    • , Ming Yan
    • , Wei Wei
    •  & Yunfeng Lu
  3. Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095, USA

    • Ming Yan
  4. Department of Medicine, Keck School of Medicine of USC, University of Southern California (USC), Los Angeles, California 90033, USA

    • Mo Yin Lau
    • , Jay Hu
    • , Hui Han
    •  & Cheng Ji
  5. School of Medicine, University of California, Los Angeles, California 90095, USA

    • Otto O. Yang
  6. Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Jiao Tong University, Shanghai 200092, China

    • Sheng Liang
    •  & Hui Wang
  7. Beijing Institute of Biotechnology, Beijing 100071, China

    • Jianmin Li
    •  & Wei Chen
  8. School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240, China

    • Xinyuan Zhu

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Contributions

M.Y., L.S., W.C., O.Y., C.J. and Y.Lu conceived or designed the experiments. Y.Liu and J.D. performed the synthesis, characterization and data analysis. M.Lau, J.H., H.H. and J.L. performed the in vivo tests. S.L., W.W., X.Z. and H.W. performed the biodistribution and pharmacokinetic studies. Y.Liu, J.D., C.J. and Y.Lu co-wrote the paper. All authors discussed the results and commented on the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Linqi Shi or Wei Chen or Cheng Ji or Yunfeng Lu.

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DOI

https://doi.org/10.1038/nnano.2012.264

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