Preliminary Study on Drug-Loaded Chondroitin Sulfate-Modified Micelles Targeting Golgi Apparatus in Tumor Cells for the Treatment of Tumor Metastasis

ZHOU Hong-li, LI Shao-hong, CHEN Dan, ZHAO Ting, GONG Tao, LI Jia

Abstract

To make preliminary exploration into the Golgi apparatus targeting of chondroitin sulfate-modified micelles (CSmicelles) co-loaded with pirarubicin (THP) and vinorelbine (VRL) in tumor cells, as well as their in vitro anti-tumor metastasis effect.   Methods  The cellular uptake efficiency and internalization mechanism of CSmicelles in 4T1 mouse breast cancer cell line were investigated by flow cytometry. Preliminary study of the Golgi apparatus targeting CSmicelles in tumor cells was conducted by co-localization experiment. Then, the effect of CSmicelles co-loaded with THP and VRL (THP+VTL-CSmicelles) on the structure of Golgi apparatus was investigated by GM130 immunofluorescence experiment. Finally, the in vitro anti-tumor metastasis ability of THP+VTL-CSmicelles was evaluated by wound healing assay and Transwell migration/invasion assay.   Results  It was found that CSmicelles could significantly increase cellular uptake of drugs. CSmicelles were internalized into cells through clathrin-mediated and caveolin-mediated endocytosis, which was energy-dependent active transport and exhibited substantial ability of targeting Golgi apparatus in tumor cells. THP+VTL-CSmicelles could break down the structure of Golgi apparatus and significantly inhibit the migration and invasion of tumor cells.  Conclusion   THP+VTL-CSmicelles demonstrate high affinity towards Golgi apparatus in tumor cells, exert targeted effects and inhibit tumor cell metastasis, which provides a novel idea and method for the treatment of cancer metastasis.

 

Keywords: Golgi apparatus targeting, Tumor metastasis, Chondroitin sulfate, Micelles, Vinorelbine

 

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