Ginsenoside Rg3 liposomes regulate tumor microenvironment for the treatment of triple negative breast cancer

Abstract

Objective

To improve the solubility and targeting of Ginsenoside Rg3 (G-Rg3), in the current study, we constructed a novel targeting functional material folic acid -poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate (FA-PEOz-CHMC, FPC) modified G-Rg3 liposomes (FPC-Rg3-L).

Methods

FPC was synthesized by using folic acid (FA) as a targeted head coupling with acid-activated poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate. The inhibitory effects of the G-Rg3 preparations on mouse breast cancer cells (4T1) were investigated by CCK-8 assay. Paraffin sections of female BALB/c mice viscera were taken for hematoxylin-eosin (H&E) staining after continuous tail vein injection of G-Rg3 preparations. BALB/c mice bearing triple-negative breast cancer (TNBC) were used as animal models to investigate the inhibition of G-Rg3 preparations on tumor growth and improving quality of life. Transforming growth factor-β1 (TGF-β1) and α-smooth muscular actin (α-SMA) were used to investigate the expression of two fibrosis factors in tumor tissues by western blotting.

Results

Compared with G-Rg3 solution (Rg3-S) and Rg3-L, FPC-Rg3-L had a significant inhibitory effect on 4T1 cells (p < .01), and the half maximal inhibitory concentration (IC₅₀) of FPC-Rg3-L was significantly lower (p < .01). The H&E results showed that the injection of FPC-Rg3-L and Rg3-S did not cause damage to the organs of mice. Compared with the control group, tumor growth was significantly inhibited in mice treated with FPC-Rg3-L and G-Rg3 solutions (p < .01).

Conclusions

This study presents a new and safe treatment for TNBC, reduces the toxic and side effects of the drug, and provides a reference for the efficient use of Chinese herbal medicine components.

Keywords:

• Liposomes
• Ginsenoside Rg3
• folic acid
• poly(2-ethyl-2-oxazoline)
• triple-negative breast cancer

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work is supported by the Natural Science Foundation of Liaoning Province (2022-MS-313), the General fund project of Liaoning Provincial Education Department (LJKZ0981) and the Open Project of Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine (TCM-201913).