Skip to main content
SpringerLink
Log in

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

  • Research Article
  • Published:
Nano Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bianchini, G.; Balko, J. M.; Mayer, I. A.; Sanders, M. E.; Gianni, L. Triple-negative breast cancer: Challenges and opportunities of a heterogeneous disease. Nat. Rev. Clin. Oncol. 2016, 13, 674–690.

    Article  CAS  Google Scholar 

  2. Foulkes, W. D.; Smith, I. E.; Reis-Filho, J. S. Triple-negative breast cancer. N. Engl. J. Med. 2010, 363, 1938–1948.

    Article  CAS  Google Scholar 

  3. Wu, Q.; Li, B.; Li, Z. Y.; Li, J. J.; Sun, S.; Sun, S. R. Cancer-associated adipocytes: Key players in breast cancer progression. J. Hematol. Oncol. 2019, 12, 95.

    Article  CAS  Google Scholar 

  4. Rybinska, I.; Agresti, R.; Trapani, A.; Tagliabue, E.; Triulzi, T. Adipocytes in breast cancer, the thick and the thin. Cells 2020, 9, 560.

    Article  CAS  Google Scholar 

  5. Bandini, E.; Rossi, T.; Gallerani, G.; Fabbri, F. Adipocytes and microRNAs crosstalk: A key tile in the mosaic of breast cancer microenvironment. Cancers (Basel) 2019, 11, 1451.

    Article  CAS  Google Scholar 

  6. Kothari, C.; Diorio, C.; Durocher, F. The importance of breast adipose tissue in breast cancer. Int. J. Mol. Sci. 2020, 21, 5760.

    Article  CAS  Google Scholar 

  7. Park, J. H.; Vithayathil, S.; Kumar, S.; Sung, P. L.; Dobrolecki, L. E.; Putluri, V.; Bhat, V. B.; Bhowmik, S. K.; Gupta, V.; Arora, K. et al. Fatty acid oxidation-driven Src links mitochondrial energy reprogramming and oncogenic properties in triple-negative breast cancer. Cell Rep. 2016, 14, 2154–2165.

    Article  CAS  Google Scholar 

  8. Van Weverwijk, A.; Koundouros, N.; Iravani, M.; Ashenden, M.; Gao, Q.; Poulogiannis, G.; Jungwirth, U.; Isacke, C. M. Metabolic adaptability in metastatic breast cancer by AKR1B10-dependent balancing of glycolysis and fatty acid oxidation. Nat. Commun. 2019, 10, 2698.

    Article  Google Scholar 

  9. Ariaans, G.; Jalving, M.; De Vries, E. G. E.; De Jong, S. Anti-tumor effects of everolimus and metformin are complementary and glucose-dependent in breast cancer cells. BMC Cancer 2017, 17, 232.

    Article  Google Scholar 

  10. Molina, J. R.; Sun, Y. T.; Protopopova, M.; Gera, S.; Bandi, M.; Bristow, C.; McAfoos, T.; Morlacchi, P.; Ackroyd, J.; Agip, A. N. A. et al. An inhibitor of oxidative phosphorylation exploits cancer vulnerability. Nat. Med. 2018, 24, 1036–1046.

    Article  CAS  Google Scholar 

  11. Ashton, T. M.; McKenna, W. G.; Kunz-Schughart, L. A.; Higgins, G. S. Oxidative phosphorylation as an emerging target in cancer therapy. Clin. Cancer Res. 2018, 24, 2482–2490.

    Article  CAS  Google Scholar 

  12. Xu, Y. Y.; Guo, Y. D.; Chen, L.; Ni, D. L.; Hu, P.; Shi, J. L. Tumor chemical suffocation therapy by dual respiratory inhibitions. Chem. Sci. 2021, 12, 7763–7769.

    Article  CAS  Google Scholar 

  13. Benjamin, D.; Colombi, M.; Hindupur, S. K.; Betz, C.; Lane, H. A.; El-Shemerly, M. Y. M.; Lu, M.; Quagliata, L.; Terracciano, L.; Moes, S. et al. Syrosingopine sensitizes cancer cells to killing by metformin. Sci. Adv. 2016, 2, 1601756.

    Article  Google Scholar 

  14. Klosowski, E. M.; De Souza, B. T. L.; Mito, M. S.; Constantin, R. P.; Mantovanelli, G. C.; Mewes, J. M.; Bizerra, P. F. V.; Menezes, P. V. M. D. C.; Gilglioni, E. H.; Utsunomiya, K. S. et al. The photodynamic and direct actions of methylene blue on mitochondrial energy metabolism: A balance of the useful and harmful effects of this photosensitizer. Free Radical Biol. Med. 2020, 153, 34–53.

    Article  CAS  Google Scholar 

  15. Lv, W.; Zhang, Z.; Zhang, K. Y.; Yang, H. R.; Liu, S. J.; Xu, A. Q.; Guo, S.; Zhao, Q.; Huang, W. A mitochondria-targeted photosensitizer showing improved photodynamic therapy effects under Hypoxia. Angew. Chem., Int. Ed. 2016, 55, 9947–9951.

    Article  CAS  Google Scholar 

  16. Huang, H. Y.; Yu, B. L.; Zhang, P. Y.; Huang, J. J.; Chen, Y.; Gasser, G.; Ji, L. N.; Chao, H. Highly charged ruthenium(II) polypyridyl complexes as lysosome-localized photosensitizers for two-photon photodynamic therapy. Angew. Chem., Int. Ed. 2015, 54, 14049–14052.

    Article  CAS  Google Scholar 

  17. Tang, Z. M.; Zhao, P. R.; Ni, D. L.; Liu, Y. Y.; Zhang, M.; Wang, H.; Zhang, H.; Gao, H. B.; Yao, Z. W.; Bu, W. B. Pyroelectric nanoplatform for NIR-II-triggered photothermal therapy with simultaneous pyroelectric dynamic therapy. Mater. Horiz. 2018, 5, 946–952.

    Article  CAS  Google Scholar 

  18. Fang, R. H.; Kroll, A. V.; Zhang, L. F. Nanoparticle-based manipulation of antigen-presenting cells for cancer immunotherapy. Small 2015, 11, 5483–5496.

    Article  CAS  Google Scholar 

  19. Zhang, D.; Wu, H. T.; Bowen, C. R.; Yang, Y. Recent advances in pyroelectric materials and applications. Small 2021, 17, 2103960.

    Article  CAS  Google Scholar 

  20. Liow, C. H.; Lu, X.; Zeng, K. Y.; Li, S. Z.; Ho, G. W. Optically governed dynamic surface charge redistribution of hybrid plasmo-pyroelectric nanosystems. Small 2019, 15, 1903042.

    Article  Google Scholar 

  21. Benke, A.; Mehner, E.; Rosenkranz, M.; Dmitrieva, E.; Leisegang, T.; Stöcker, H.; Pompe, W.; Meyer, D. C. Pyroelectrically driven ·OH generation by barium titanate and palladium nanoparticles. J. Phys. Chem. C 2015, 119, 18278–18286.

    Article  CAS  Google Scholar 

  22. Chang, Y.; Cheng, Y.; Zheng, R. X.; Wu, X. Q.; Song, P. P.; Wang, Y. J.; Yan, J.; Zhang, H. Y. Plasmon-pyroelectric nanostructures used to produce a temperature-mediated reactive oxygen species for hypoxic tumor therapy. Nano Today 2021, 38, 101110.

    Article  CAS  Google Scholar 

  23. Hao, F.; Nehl, C. L.; Hafner, J. H.; Nordlander, P. Plasmon resonances of a gold nanostar. Nano Lett. 2007, 7, 729–732.

    Article  CAS  Google Scholar 

  24. Huang, X. H.; El-Sayed, I. H.; Qian, W.; El-Sayed, M. A. Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. J. Am. Chem. Soc. 2006, 128, 2115–2120.

    Article  CAS  Google Scholar 

  25. Skrabalak, S. E.; Chen, J. Y.; Au, L.; Lu, X. M.; Li, X. D.; Xia, Y. N. Gold nanocages for biomedical applications. Adv. Mater. 2007, 19, 3177–3184.

    Article  CAS  Google Scholar 

  26. Čulić-Viskota, J.; Dempsey, W. P.; Fraser, S. E.; Pantazis, P. Surface functionalization of barium titanate SHG nanoprobes for in vivo imaging in zebrafish. Nat. Protoc. 2012, 7, 1618–1633.

    Article  Google Scholar 

  27. Brinson, B. E.; Lassiter, J. B.; Levin, C. S.; Bardhan, R.; Mirin, N.; Halas, N. J. Nanoshells made easy: Improving Au layer growth on nanoparticle surfaces. Langmuir 2008, 24, 14166–14171.

    Article  CAS  Google Scholar 

  28. Ok, K. M.; Chi, E. O.; Halasyamani, P. S. Bulk characterization methods for non-centrosymmetric materials: Second-harmonic generation, piezoelectricity, pyroelectricity, and ferroelectricity. Chem. Soc. Rev. 2006, 35, 710–717.

    Article  CAS  Google Scholar 

  29. Haertling, G. H. Ferroelectric ceramics: History and technology. J. Am. Ceram. Soc. 1999, 82, 797–818.

    Article  CAS  Google Scholar 

  30. Roper, D. K.; Ahn, W.; Hoepfner, M. Microscale heat transfer transduced by surface plasmon resonant gold nanoparticles. J. Phys. Chem. C 2007, 111, 3636–3641.

    Article  CAS  Google Scholar 

  31. Richter, K.; Haslbeck, M.; Buchner, J. The heat shock response: Life on the verge of death. Mol. Cell 2010, 40, 253–266.

    Article  CAS  Google Scholar 

  32. Nel, A.; Xia, T.; Mädler, L.; Li, N. Toxic potential of materials at the nanolevel. Science 2006, 311, 622–627.

    Article  CAS  Google Scholar 

  33. Feng, Y. L.; Wang, G. R.; Chang, Y.; Cheng, Y.; Sun, B. B.; Wang, L. M.; Chen, C. Y.; Zhang, H. Y. Electron compensation effect suppressed silver Ion release and contributed safety of Au@Ag core—shell nanoparticles. Nano Lett. 2019, 19, 4478–4489.

    Article  CAS  Google Scholar 

Download references

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.

Author information

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jianlin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xin Ning
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aiyun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qing You
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wanzhen Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Deping Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jianyun Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lan Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Fangfang Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Xiaoyuan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jimin Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Fangfang Cao, Xiaoyuan Chen or Jimin Cao.

Electronic Supplementary Material

12274_2022_4927_MOESM1_ESM.pdf

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

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

Keywords

Search

Navigation