文献类型：期刊文献

英文题名：Glutathione-responsive core cross-linked micelles for controlled cabazitaxel delivery

作者：Han, Xiaoxiong[1];Gong, Feirong[2];Sun, Jing[1];Li, Yueqi[3];Liu, XiaoFei[1];Chen, Dan[1];Liu, Jianwen[3];Shen, Yaling[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai Collaborat Innovat Ctr Biomfg Technol, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Mat Sci & Engn, Key Lab Ultrafine Mat, Minist Educ, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai Key Lab Chem Biol, Sch Pharm, Shanghai 200237, Peoples R China

年份：2018

卷号：20

期号：2

外文期刊名：JOURNAL OF NANOPARTICLE RESEARCH

收录：;EI(收录号：20180804826448);WOS:【SCI-EXPANDED(收录号:WOS:000425382300001)】；

基金：This work was supported by the National Natural Science Foundation of China (No. 81673969). We are grateful to Yueqi Li and Cen Qiu (School of Pharmacy, East China University of Science and Technology) for the help in completing the experiments about MCF-7 cells.

语种：英文

外文关键词：Cabazitaxel; Glutathione-responsive; Polymeric micelles; Solubility; Endocytosis mechanism; Biomedicine

摘要：Stimulus-responsive polymeric micelles (PMs) have recently received attention due to the controlled delivery of drug or gene for application in cancer diagnosis and treatment. In this work, novel glutathione-responsive PMs were prepared to encapsulate hydrophobic antineoplastic drug, cabazitaxel (CTX), to improve its solubility and toxicity. These CTX-loaded micelles core cross-linked by disulfide bonds (DCL-CTX micelles) were prepared by a novel copolymer, lipoic acid grafted mPEG-PLA. These micelles had regular spherical shape, homogeneous diameter of 18.97 +/- 0.23 nm, and a narrow size distribution. The DCL-CTX micelles showed high encapsulation efficiency of 98.65 +/- 1.77%, and the aqueous solubility of CTX was improved by a factor of 1:1200. In vitro release investigation showed that DCL-CTX micelles were stable in the medium without glutathione (GSH), whereas the micelles had burst CTX release in the medium with 10 mM GSH. Cell uptake results implied that DCL-CTX micelles were internalized into MCF-7 cells through clathrin-mediated endocytosis and released cargo more effectively than Jevtana (commercially available CTX) owing to GSH-stimulated degradation. In MTT assay against MCF-7 cells, these micelles inhibited tumor cell proliferation more effectively than Jevtana due to their GSH-responsive CTX release. All results revealed the potency of GSH-responsive DCL-CTX micelles for stable delivery in blood circulation and for intracellular GSH-trigged release of CTX. Therefore, DCL-CTX micelles show potential as safe and effective CTX delivery carriers and as a cancer chemotherapy formulation.