期刊
BIOMATERIALS
卷 271, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.120716
关键词
Breast cancer; Doxorubicin-exacerbated metastasis; Co-assembled nanodrug; Berberine; HMGB1
资金
- 13th Fiveyear Plan Science and Technology Project, Department of Education of Jilin Province [JJKH20201037K]
- Capital Construction Funds for Innovation Capacity Building, Jilin Provincial Development and Reform Commission [2020C0341]
- Fundamental Research Funds for the Central Universities
Chemotherapy is a double-edged sword in treating breast cancer, as it can induce cancer progression; Berberine has shown potential as a regulator for Dox-exacerbated breast cancer metastasis by targeting the HMGB1-TLR4 axis; The combination of Dox and Ber in a self-assembled nanodrug can effectively inhibit tumor growth and metastasis.
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.
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