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

作　　者：Xin-yue DONG Tian-qun LANG Qi YIN Peng-cheng ZHANG Ya-ping LI 

机构地区：[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

出　　处：《Acta Pharmacologica Sinica》2017年第12期1655-1662,共8页中国药理学报（英文版）

基　　金：The National Basic Research Program of China （2014CB931900）, the National Natural Science Foundation of China （81521005 81230029）, and the Youth Innovation Promotion Association of CAS （2015226） are gratefully acknowledged for financial support.

摘　　要：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±0.4nm, 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 anti- metastasis 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.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±0.4nm, 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 anti- metastasis 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.

关 键 词：pH-sensitive polymer CO-DELIVERY MICELLE DOCETAXEL SILIBININ breast cancer mouse breast cancer cell line 4T1 metastasis 

分 类 号：R0[医药卫生]