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Metastasis remains the primary cause for mortality of breast cancer. Despite advances in current therapeutic agents, patients with metastatic breast cancer still have poor prognoses. Tumor hypoxia, a key microenvironment factor, is emerging as an attractive target to prevent metastasis and is also involved with resistance to phototherapy. Here, we show an effective nanotherapeutic approach based on manganese dioxide-coated polydopamine nanocarriers to trigger robust anti-tumor and anti-metastasis responses against metastatic breast cancer by supplemental oxygenation and multimodal imaging-guided phototherapies. In cancer cells, the produced oxygen by the developed nanoplatform decreases the expression of hypoxia-inducible factors 1α to inhibit tumor metastasis, and enhances the efficacy of photodynamic therapy. This nanotherapeutic approach enables the combined photodynamic/ photothermal treatments with great inhibition on cell migration and invasion in vitro. Moreover, the nanotherapeutics effectively suppresses primary tumor progress and inhibits lung metastasis in vivo in a breast cancer mouse model with satisfying biosafety. This study suggests that the tumor hypoxia-targeting nanotherapeutics have great potential for preventing and treating metastatic cancers.


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Effective nanotherapeutic approach for metastatic breast cancer treatment by supplemental oxygenation and imaging-guided phototherapy

Show Author's information Jialing HuFuan WangFeng LiuWentong SunQunying JiangYahua LiuYun ZhaoXiaoqing Liu( )
Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China

Abstract

Metastasis remains the primary cause for mortality of breast cancer. Despite advances in current therapeutic agents, patients with metastatic breast cancer still have poor prognoses. Tumor hypoxia, a key microenvironment factor, is emerging as an attractive target to prevent metastasis and is also involved with resistance to phototherapy. Here, we show an effective nanotherapeutic approach based on manganese dioxide-coated polydopamine nanocarriers to trigger robust anti-tumor and anti-metastasis responses against metastatic breast cancer by supplemental oxygenation and multimodal imaging-guided phototherapies. In cancer cells, the produced oxygen by the developed nanoplatform decreases the expression of hypoxia-inducible factors 1α to inhibit tumor metastasis, and enhances the efficacy of photodynamic therapy. This nanotherapeutic approach enables the combined photodynamic/ photothermal treatments with great inhibition on cell migration and invasion in vitro. Moreover, the nanotherapeutics effectively suppresses primary tumor progress and inhibits lung metastasis in vivo in a breast cancer mouse model with satisfying biosafety. This study suggests that the tumor hypoxia-targeting nanotherapeutics have great potential for preventing and treating metastatic cancers.

Keywords: hypoxia, nanomedicine, breast cancer metastasis, supplemental oxygenation, phototherapy

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Publication history
Copyright
Acknowledgements

Publication history

Received: 24 December 2019
Revised: 08 March 2020
Accepted: 09 March 2020
Published: 30 March 2020
Issue date: April 2020

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

Acknowledgements

This work is supported by the National Natural Science Foundation of China (Nos. 81602610 and 21874103), and Fundamental Research Funds for the Central Universities (Nos. 2042018kf1006 and 2042018kf0210).

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