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Nano Research 2022, 15(7): 6278-6287 https://doi.org/10.1007/s12274-022-4237-2
Research Article | Issue | Published: 20 April 2022

Dual inhibition of glycolysis and oxidative phosphorylation by aptamer-based artificial enzyme for synergistic cancer therapy

Show Author's Information Xiao Fang1,  Meng Yuan1,  Junduan Dai1,  Qianying Lin1,  Yuhong Lin1,  Wenli Wang1,  Yifan Jiang1,  Haihui Wang1,  Fang Zhao1,  Junye Wu1,  Shumeng Bai2,  Chunhua Lu1( ),  Huanghao Yang1( )
MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350108, China
College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, China
Keywords:
cancer therapy, photochemistry, aptamers, artificial enzymes, energy blockage
Topics:
Biochemistry
Cite this article:
Fang X, Yuan M, Dai J, et al. Dual inhibition of glycolysis and oxidative phosphorylation by aptamer-based artificial enzyme for synergistic cancer therapy. Nano Research, 2022, 15(7): 6278-6287. https://doi.org/10.1007/s12274-022-4237-2
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Abstract Full text Electronic supplementary material About this article

Dual inhibition of glycolysis and oxidative phosphorylation (OXPHOS) can break the metabolic plasticity of cancer cells to inhibit most energy supply and lead to effective cancer therapy. However, the pharmacokinetic difference among drugs hinders these two inhibitions to realize a uniform temporal and spatial distribution. Herein, we report an aptamer-based artificial enzyme for simultaneous dual inhibition of glycolysis and OXPHOS, which is constructed by arginine aptamer modified carbon-dots-doped graphitic carbon nitride (AptCCN). AptCCN can circularly capture intracellular arginine attribute to the specific binding ability of arginine aptamers to arginine, and further catalyze the oxidation of enriched arginine to nitric oxide (NO) under red light irradiation. In vitro and in vivo experiments showed that arginine depletion and NO stress could inhibit glycolysis and OXPHOS, leading to energy blockage and apoptosis of cancer cells. The presented aptamer-based artificial enzyme strategy provides a new path for cell pathway regulation and synergistic cancer therapy.


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Abstract
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Electronic supplementary material
About this article

Dual inhibition of glycolysis and oxidative phosphorylation by aptamer-based artificial enzyme for synergistic cancer therapy

Show Author's information Xiao Fang1, Meng Yuan1, Junduan Dai1, Qianying Lin1, Yuhong Lin1, Wenli Wang1, Yifan Jiang1, Haihui Wang1, Fang Zhao1, Junye Wu1, Shumeng Bai2, Chunhua Lu1( ), Huanghao Yang1( )
MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350108, China
College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, China

Abstract

Dual inhibition of glycolysis and oxidative phosphorylation (OXPHOS) can break the metabolic plasticity of cancer cells to inhibit most energy supply and lead to effective cancer therapy. However, the pharmacokinetic difference among drugs hinders these two inhibitions to realize a uniform temporal and spatial distribution. Herein, we report an aptamer-based artificial enzyme for simultaneous dual inhibition of glycolysis and OXPHOS, which is constructed by arginine aptamer modified carbon-dots-doped graphitic carbon nitride (AptCCN). AptCCN can circularly capture intracellular arginine attribute to the specific binding ability of arginine aptamers to arginine, and further catalyze the oxidation of enriched arginine to nitric oxide (NO) under red light irradiation. In vitro and in vivo experiments showed that arginine depletion and NO stress could inhibit glycolysis and OXPHOS, leading to energy blockage and apoptosis of cancer cells. The presented aptamer-based artificial enzyme strategy provides a new path for cell pathway regulation and synergistic cancer therapy.

Keywords: cancer therapy, photochemistry, aptamers, artificial enzymes, energy blockage

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Publication history
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Acknowledgements

Publication history

Received: 16 December 2021
Revised: 12 February 2022
Accepted: 13 February 2022
Published: 20 April 2022
Issue date: July 2022

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

This work was supported by the National Key Research and Development Program of China (Nos. 2018YFA0902600 and 2020YFA0210800), the National Natural Science Foundation of China (Nos. 22174019, 21775025, U1705281, and 22027805), the Natural Science Foundation of Fujian (No. 2020J06036), and the Major Project of Science and Technology of Fujian Province (No. 2020HZ06006).

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