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

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

来源：Biomaterials, 2021, 271: 120716.

DOI：10.1016/j.biomaterials.2021.120716

• Breast cancer
• Doxorubicin-exacerbated metastasis
• Co-assembled nanodrug
• Berberine
• HMGB1

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.

• 单位
  吉林大学