2. Academic Validation
  3. Targeting therapy and tumor microenvironment remodeling of triple-negative breast cancer by ginsenoside Rg3 based liposomes

Targeting therapy and tumor microenvironment remodeling of triple-negative breast cancer by ginsenoside Rg3 based liposomes

  • J Nanobiotechnology. 2022 Sep 15;20(1):414. doi: 10.1186/s12951-022-01623-2.
Jiaxuan Xia 1,  Shuya Zhang 1,  Ru Zhang 1,  Anni Wang 1,  Ying Zhu 2,  Meichen Dong 1,  Shaojie Ma 3,  Chao Hong 4,  Shengyao Liu 1,  Dan Wang 5,  Jianxin Wang 6 7
Affiliations

Affiliations

  • 1 Department of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 201203, China.
  • 2 Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
  • 3 Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430071, China.
  • 4 Experiment Center of Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 5 Xiamen Ginposome Pharmatech Co., Ltd, Xiamen, 361026, People's Republic of China.
  • 6 Department of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 201203, China. jxwang@fudan.edu.cn.
  • 7 Institutes of Integrative Medicine, Fudan University, Shanghai, 201203, People's Republic of China. jxwang@fudan.edu.cn.
PMID: 36109762 DOI: 10.1186/s12951-022-01623-2
Abstract

The chemotherapy effect of docetaxel (DTX) against triple-negative breast Cancer (TNBC) remains mediocre and limited when encapsulated in conventional Cholesterol liposomes, mainly ascribed to poor penetration and immunosuppressive tumor microenvironment (TME) caused by tumor stroma cells, especially cancer-associated fibroblasts (CAFs). Many studies have attempted to address these problems but trapped into the common dilemma of excessively complicated formulation strategies at the expense of druggability as well as clinical translational feasibility. To better address the discrepancy, ginsenoside Rg3 was utilized to substitute Cholesterol to develop a multifunctional DTX-loaded Rg3 Liposome (Rg3-Lp/DTX). The obtained Rg3-Lp/DTX was proved to be preferentially uptake by 4T1 cells and accumulate more at tumor site via the interaction between the glycosyl moiety of Rg3 exposed on Liposome surface and glucose transporter1 (GLUT1) overexpressed on tumor cells. After reaching tumor site, Rg3 was shown to reverse the activated CAFs to the resting stage and attenuate the dense stroma barrier by suppressing secretion of TGF-β from tumor cells and regulating TGF-β/Smad signaling. Therefore, reduced levels of CAFs and collagens were found in TME after incorporation of Rg3, inducing enhanced penetration of Rg3-Lp/DTX in the tumor and reversed immune system which can detect and neutralize tumor cells. Compared with wooden Cholesterol liposomes, the smart and versatile Rg3-Lp/DTX could significantly improve the anti-tumor effect of DTX, providing a promising approach for TNBC therapy with excellent therapeutic efficacy and simple preparation process.

Keywords

Cancer-associated fibroblasts; Docetaxel; Ginsenoside Rg3; Liposomes; Stroma cells; Triple-negative breast cancer; Tumor active targeting; Tumor microenvironment.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-19331
    99.93%, Glut1抑制剂
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