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Nano Research 2022, 15(6): 5273-5278 https://doi.org/10.1007/s12274-022-4166-0
Research Article | Issue | Published: 15 March 2022

Specific generation of nitric oxide in mitochondria of cancer cell for selective oncotherapy

Show Author's Information Mengyu Sun1,2,§,  Yanjuan Sang1,2,§,  Qingqing Deng1,2,  Zhengwei Liu1,3,  Jinsong Ren1,2( ),  Xiaogang Qu1,2( )
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
University of Chinese Academy of Sciences, Beijing 100039, China

§ Mengyu Sun and Yanjuan Sang contributed equally to this work.

Keywords:
mitochondria, nanozyme, nitric oxide, nitric oxide synthetase, specific cancer therapy
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Nano biology
Cite this article:
Sun M, Sang Y, Deng Q, et al. Specific generation of nitric oxide in mitochondria of cancer cell for selective oncotherapy. Nano Research, 2022, 15(6): 5273-5278. https://doi.org/10.1007/s12274-022-4166-0
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Abstract Full text Electronic supplementary material About this article

Nitric oxide (NO) gas therapy, especially, L-arginine (L-Arg)-based NO treatment strategies have attracted extensive attention in the field of oncotherapy. However, current strategies are unable to differentiate well between normal cells and cancer cells, which may lead to unpredictable toxicity. Motivated by the fact that mitochondria of cancer cells can express excessive nitric oxide synthetase (NOS), herein, a nanozyme-based NO generator, cerium oxide (CeO2)-AT, is fabricated to specifically catalyze the production of NO in cancer cells for selective tumor treatment. In this system, after being endocytosed into cancer cells, the generator can produce a number of NO under the catalysis of NOS in mitochondria of cancer cells, which can disrupt the mitochondrial respiratory chain of tumor cells and further induce cell apoptosis. In addition, the generator with catalase (CAT)-like activity can catalyze H2O2 to produce O2, which can promote the generation of NO and improve the performance of NO gas therapy. What is more, our system has no obvious impact on the viability of normal cells owing to the less production of NO. Our work paves a new way for the development of highly selective NO-based treatment particularly useful for the safe and specific cancer therapy.


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Abstract
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Electronic supplementary material
About this article

Specific generation of nitric oxide in mitochondria of cancer cell for selective oncotherapy

Show Author's information Mengyu Sun1,2,§, Yanjuan Sang1,2,§, Qingqing Deng1,2, Zhengwei Liu1,3, Jinsong Ren1,2( ), Xiaogang Qu1,2( )
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
University of Chinese Academy of Sciences, Beijing 100039, China

§ Mengyu Sun and Yanjuan Sang contributed equally to this work.

Abstract

Nitric oxide (NO) gas therapy, especially, L-arginine (L-Arg)-based NO treatment strategies have attracted extensive attention in the field of oncotherapy. However, current strategies are unable to differentiate well between normal cells and cancer cells, which may lead to unpredictable toxicity. Motivated by the fact that mitochondria of cancer cells can express excessive nitric oxide synthetase (NOS), herein, a nanozyme-based NO generator, cerium oxide (CeO2)-AT, is fabricated to specifically catalyze the production of NO in cancer cells for selective tumor treatment. In this system, after being endocytosed into cancer cells, the generator can produce a number of NO under the catalysis of NOS in mitochondria of cancer cells, which can disrupt the mitochondrial respiratory chain of tumor cells and further induce cell apoptosis. In addition, the generator with catalase (CAT)-like activity can catalyze H2O2 to produce O2, which can promote the generation of NO and improve the performance of NO gas therapy. What is more, our system has no obvious impact on the viability of normal cells owing to the less production of NO. Our work paves a new way for the development of highly selective NO-based treatment particularly useful for the safe and specific cancer therapy.

Keywords: mitochondria, nanozyme, nitric oxide, nitric oxide synthetase, specific cancer therapy

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Publication history
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Acknowledgements

Publication history

Received: 04 December 2021
Revised: 12 January 2022
Accepted: 13 January 2022
Published: 15 March 2022
Issue date: April 2022

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

This work was supported by the National Key R&D Program of China (No. 2021YFF1200701), the National Natural Science Foundation of China (Nos. 91856205, 21820102009, and 21871249), and the Key Program of Frontier of Sciences (No. CAS QYZDJ-SSW-SLH052). The authors declare no competing financial interest. The animal study protocol was approved by the Institutional Animal Care and Use Committee at Jilin University.

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