Glutathione-responsive core cross-linked micelles for controlled cabazitaxel delivery

  • Xiaoxiong Han
  • Feirong Gong
  • Jing Sun
  • Yueqi Li
  • XiaoFei Liu
  • Dan Chen
  • Jianwen Liu
  • Yaling Shen
Research Paper


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.


Cabazitaxel Glutathione-responsive Polymeric micelles Solubility Endocytosis mechanism Biomedicine 



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.

Compliance with ethical standards

Conflict of interest

The authors confirm that there are no conflicts of interest.

Supplementary material

11051_2018_4128_MOESM1_ESM.pdf (387 kb)
ESM 1 (PDF 387 kb)


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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Xiaoxiong Han
    • 1
  • Feirong Gong
    • 2
  • Jing Sun
    • 1
  • Yueqi Li
    • 3
  • XiaoFei Liu
    • 1
  • Dan Chen
    • 1
  • Jianwen Liu
    • 3
  • Yaling Shen
    • 1
  1. 1.State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing TechnologyEast China University of Science and TechnologyShanghaiChina
  2. 2.Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and EngineeringEast China University of Science and TechnologyShanghaiChina
  3. 3.State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of PharmacyEast China University of Science and TechnologyShanghaiChina

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