Original Article

Co-delivery of docetaxel and silibinin using pH-sensitive micelles improves therapy of metastatic breast cancer

Authors: Xin-yue DONG1, Tian-qun LANG2, Qi YIN2, Peng-cheng ZHANG2, Ya-ping LI2
1 Nano Science and Technology Institute, University of Science and Technology of China, Suzhou 215123, China
2 State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Corresponding to: Qi YIN: qyin@simm.ac.cn, Ya-ping LI: ypli@simm.ac.cn,
DOI: 10.1038/aps.2017.74
Received: 5 March 2017
Accepted: 4 April 2017
Advance online: 17 July 2017


Breast cancer is the most vicious killer for women, and tumor metastasis is one of the leading causes of breast cancer therapy failure. In this study, a new pH-sensitive polymer (polyethylene glycol-block-poly[(1,4-butanediol)-diacrylate-β-N,N-diisopropylethylenediamine], BDP) was synthesized. Based on BDP, docetaxel/silibinin co-delivery micelles (DSMs) was constructed. DSM had a well-defined spherical shape under the transmission electron microscope with average hydrodynamic diameter of 85.3±0.4 nm, and were stable in the bloodstream but could dissociate to release the chemotherapeutic agents in the low pH environment of the endo/lysosomes in the tumor cells. Compared with free drugs, DSM displayed greatly enhanced cellular uptake, higher cytotoxicity and a stronger antimetastasis effect against mouse breast cancer cell line 4T1. In 4T1 tumor-bearing mice treated with DSM (twice a week for 3 weeks), the inhibition rate on tumor growth and metastasis reached 71.9% and 80.1%, respectively. These results reveal that DSM might be a promising drug delivery system for metastatic breast cancer therapy.
Keywords: pH-sensitive polymer; co-delivery; micelle; docetaxel; silibinin; breast cancer; mouse breast cancer cell line 4T1; metastasis