Biomimetic co-assembled nanodrug of doxorubicin and berberine suppresses chemotherapy-exacerbated breast cancer metastasis

Xiao Zheng; Yawei Zhao; Yong Jia; Dan Shao; Fan Zhang; Madi Sun; Jianati Dawulieti; Hanze Hu; Lianzhi Cui; Yue Pan; Chao Yang; Wen Sun; Shuang Zhang; Kan He; Jing Li; Jinzhi Du; Ming Zhang; Li Chen

doi:10.1016/j.biomaterials.2021.120716

Biomimetic co-assembled nanodrug of doxorubicin and berberine suppresses chemotherapy-exacerbated breast cancer metastasis

Biomaterials. 2021 Apr:271:120716. doi: 10.1016/j.biomaterials.2021.120716. Epub 2021 Feb 18.

Authors

Xiao Zheng¹, Yawei Zhao², Yong Jia², Dan Shao³, Fan Zhang¹, Madi Sun¹, Jianati Dawulieti¹, Hanze Hu⁴, Lianzhi Cui⁵, Yue Pan⁶, Chao Yang⁷, Wen Sun⁶, Shuang Zhang², Kan He², Jing Li², Jinzhi Du⁸, Ming Zhang⁹, Li Chen¹⁰

Affiliations

¹ Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences and School of Nursing, Jilin University, Changchun, 130021, China; Institutes for Life Sciences, School of Biomedical Sciences and Engineering, Guangzhou International Campus, National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510630, China.
² Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences and School of Nursing, Jilin University, Changchun, 130021, China.
³ Institutes for Life Sciences, School of Biomedical Sciences and Engineering, Guangzhou International Campus, National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510630, China; Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA. Electronic address: shaodan@scut.edu.cn.
⁴ Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA.
⁵ Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences and School of Nursing, Jilin University, Changchun, 130021, China; Clinical Laboratory, Jilin Cancer Hospital, Changchun, 130012, China.
⁶ School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, China.
⁷ Institutes for Life Sciences, School of Biomedical Sciences and Engineering, Guangzhou International Campus, National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510630, China; Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA. Electronic address: chaoyang@scut.edu.cn.
⁸ Institutes for Life Sciences, School of Biomedical Sciences and Engineering, Guangzhou International Campus, National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510630, China.
⁹ Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences and School of Nursing, Jilin University, Changchun, 130021, China. Electronic address: hangming99@jlu.edu.cn.
¹⁰ Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences and School of Nursing, Jilin University, Changchun, 130021, China. Electronic address: chenl@jlu.edu.cn.

PMID: 33621894
DOI: 10.1016/j.biomaterials.2021.120716

Abstract

Chemotherapy is a major approach for treating breast cancer patients. Paradoxically, it can also induce cancer progression. Understanding post-chemotherapy metastasis mechanism will help the development of new therapeutic strategies to ameliorate chemotherapy-induced cancer progression. In this study, we deciphered the role of HMGB1 in the regulation of TLR4-mediated epithelial to mesenchymal transitions (EMT) process on doxorubicin (Dox)-treated 4T1 breast cancer cells. Berberine (Ber), a clinically approved alkaloid has been demonstrated as an HMGB1-TLR4 axis regulator to Dox-exacerbated breast cancer metastasis in vitro and in vivo. Hypothesizing that combination of Dox and Ber would be beneficial for breast cancer chemotherapy, we engineered self-assembled nanodrug (DBNP) consisting of Dox and Ber without the aid of additional carriers. After cloaking with 4T1 cell membranes, DBNP@CM exhibited higher accumulation at tumor sites and prolonged blood circulation time in 4T1 orthotopic tumor-bearing mice than DBNP. Importantly, DBNP@CM not only effectively inhibited tumor growth with fewer side effects, but also remarkably suppressed pulmonary metastasis via blocking HMGB1-TLR4 axis. Together, our results have provided a promising combination strategy to dampen chemotherapy-exacerbated breast cancer metastasis and shed light on the development of biomimetic nanodrug for efficient and safe breast cancer chemotherapy.

Keywords: Berberine; Breast cancer; Co-assembled nanodrug; Doxorubicin-exacerbated metastasis; HMGB1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Berberine*
Biomimetics
Breast Neoplasms* / drug therapy
Cell Line, Tumor
Doxorubicin
Humans
Lung Neoplasms*
Mice
Mice, Inbred BALB C
Nanoparticles*

Substances

Berberine
Doxorubicin