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

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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Figure 1: Synthesis of enzyme nanocomplexes.
Figure 2: Structure and enhanced activity and stability of enzyme nanocomplexes.
Figure 3: In vivo detoxifying capability of the catalase-containing enzyme nanocomplexes.
Figure 4: Efficacy of n(AOx–Cat) as a prophylactic and antidote 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).

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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.

Corresponding authors

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

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The authors declare no competing financial interests.

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Liu, Y., Du, J., Yan, M. et al. Biomimetic enzyme nanocomplexes and their use as antidotes and preventive measures for alcohol intoxication. Nature Nanotech 8, 187–192 (2013). https://doi.org/10.1038/nnano.2012.264

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