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BaTiO3@Au nanoheterostructure suppresses triple-negative breast cancer by persistently disrupting mitochondrial energy metabolism

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Abstract

Abnormal metabolism has become a potential target for highly malignant and invasive triple-negative breast cancer (TNBC) due to its relatively low response to traditional therapeutics. The existing metabolic interventions demonstrated unsatisfactory therapeutic outcomes and potential systemic toxicity, resulting from the metabolic instability and limited targeting ability of inhibitors as well as complex tumor microenvironment. To address these limitations, here we developed a robust pyroelectric BaTiO3@Au core—shell nanostructure (BTO@Au) to selectively and persistently block energy generation of tumor cells. Stimulated by near-infrared (NIR) laser, the Au shell could generate heat to activate the BaTiO3 core to produce reactive oxygen species (ROS) regardless of the constrained microenvironment, thus prominently inhibits mitochondrial oxidative phosphorylation (OXPHOS) and reduces ATP production to induce TNBC cell apoptosis. The therapeutic effects have been well demonstrated in vitro and in vivo, paving a new way for the development of metabolic interventions.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 22007063 and 82002063), Shanxi Medical Key Science and Technology Project Plan of China (No. 2020XM01), the National University of Singapore Start-up Grant (No. NUHSRO/2020/133/Startup/08), NUS School of Medicine Nanomedicine Translational Research Program (No. NUHSRO/2021/034/TRP/09/Nanomedicine), the Science Research Start-up Fund for Doctor of Shanxi Province (No. XD1809 and XD2011), the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi (No. 2019L0414), and Shanxi Province Science Foundation for Youths (No. 201901D211316). The authors would like to thank Chengdu Lilai Biotechnology Co., Ltd. for the cellular TEM measurement.

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Author notes

  1. Yanlin Fengand Jianlin Wang contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, 030001, China

    Yanlin Feng, Jianlin Wang, Xin Ning, Aiyun Li, Wanzhen Su, Deping Wang, Jianyun Shi, Lan Zhou & Jimin Cao

  2. Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore, 119074, Singapore

    Qing You, Fangfang Cao & Xiaoyuan Chen

  3. Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore

    Xiaoyuan Chen

  4. Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore

    Fangfang Cao & Xiaoyuan Chen

Authors
  1. Yanlin Feng
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  2. Jianlin Wang
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  3. Xin Ning
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  9. Lan Zhou
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  10. Fangfang Cao
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Corresponding authors

Correspondence to Fangfang Cao, Xiaoyuan Chen or Jimin Cao.

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12274_2022_4927_MOESM1_ESM.pdf

BaTiO3@Au nanoheterostructure suppresses triple-negative breast cancer by persistently disrupting mitochondrial energy metabolism

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Feng, Y., Wang, J., Ning, X. et al. BaTiO3@Au nanoheterostructure suppresses triple-negative breast cancer by persistently disrupting mitochondrial energy metabolism. Nano Res. 16, 2775–2785 (2023). https://doi.org/10.1007/s12274-022-4927-9

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  • DOI: https://doi.org/10.1007/s12274-022-4927-9

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