Systemic metastasis-targeted nanotherapeutic reinforces tumor surgical resection and chemotherapy

Minjun Xu, Kaili Hu, Yipu Liu, Yukun Huang, Shanshan Liu, Yu Chen, Dayuan Wang, Songlei Zhou, Qian Zhang, Ni Mei, Huiping Lu, Fengan Li, Xiaoling Gao () and Jun Chen ()
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Minjun Xu: Fudan University
Kaili Hu: Shanghai University of Traditional Chinese Medicine
Yipu Liu: Fudan University
Yukun Huang: Fudan University
Shanshan Liu: Fudan University
Yu Chen: Fudan University
Dayuan Wang: Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine
Songlei Zhou: Fudan University
Qian Zhang: Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine
Ni Mei: Shanghai Center for Drug Evaluation and Inspection
Huiping Lu: Fudan University
Fengan Li: Fudan University
Xiaoling Gao: Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine
Jun Chen: Fudan University

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract Failure of conventional clinical therapies such as tumor resection and chemotherapy are mainly due to the ineffective control of tumor metastasis. Metastasis consists of three steps: (i) tumor cells extravasate from the primary sites into the circulation system via epithelial-mesenchymal transition (EMT), (ii) the circulating tumor cells (CTCs) form “micro-thrombi” with platelets to evade the immune surveillance in circulation, and (iii) the CTCs colonize in the pre-metastatic niche. Here, we design a systemic metastasis-targeted nanotherapeutic (H@CaPP) composed of an anti-inflammatory agent, piceatannol, and an anti-thrombotic agent, low molecular weight heparin, to hinder the multiple steps of tumor metastasis. H@CaPP is found efficiently impeded EMT, inhibited the formation of “micro-thrombi”, and prevented the development of pre-metastatic niche. When combined with surgical resection or chemotherapy, H@CaPP efficiently inhibits tumor metastasis and prolonged overall survival of tumor-bearing mice. Collectively, we provide a simple and effective systemic metastasis-targeted nanotherapeutic for combating tumor metastasis.

Date: 2021
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DOI: 10.1038/s41467-021-23466-5

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