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Updated: Aug 28, 2025
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Targeting therapy and tumor microenvironment remodeling of triple-negative breast cancer by ginsenoside Rg3 based
Jiaxuan Xia1, Shuya Zhang1, Ru Zhang1
1Department of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 201203, China.
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.
Insights
Ginsenoside Rg3 liposomes enhance docetaxel delivery for triple-negative breast cancer (TNBC) by improving tumor penetration and overcoming immunosuppression. This novel approach offers a promising, simplified strategy for more effective TNBC therapy.
Area of Science:
- Nanomedicine
- Cancer Therapy
- Drug Delivery
Background:
- Docetaxel (DTX) efficacy against triple-negative breast cancer (TNBC) is limited by poor tumor penetration and an immunosuppressive tumor microenvironment (TME).
- Conventional liposomal formulations often face challenges with complex preparation and limited clinical translation.
- Cancer-associated fibroblasts (CAFs) contribute to a dense stroma, hindering drug delivery and immune surveillance in TNBC.
Purpose of the Study:
- To develop a multifunctional docetaxel-loaded liposome using ginsenoside Rg3 to overcome the limitations of conventional liposomes in TNBC treatment.
- To investigate the enhanced tumor penetration, CAF modulation, and anti-tumor efficacy of the novel Rg3-liposome formulation.
Main Methods:
- Formulation of docetaxel-loaded Rg3 liposomes (Rg3-Lp/DTX) by substituting cholesterol with ginsenoside Rg3.
- Evaluation of cellular uptake via interaction between Rg3 and glucose transporter 1 (Glut1) on 4T1 cells.
- Assessment of CAF modulation, stroma reduction, and anti-tumor effects in the TME.
Main Results:
- Rg3-Lp/DTX demonstrated preferential uptake by 4T1 cells and enhanced accumulation at the tumor site.
- Ginsenoside Rg3 reversed activated CAFs to a resting state, reducing dense stroma and TGF-β signaling.
- Rg3-Lp/DTX significantly improved DTX anti-tumor efficacy compared to conventional cholesterol liposomes, enhancing tumor penetration and immune response.
Conclusions:
- The multifunctional Rg3-Lp/DTX formulation offers a simplified and effective approach for TNBC therapy.
- This strategy enhances drug delivery by improving tumor penetration and modulating the immunosuppressive TME.
- Rg3-Lp/DTX presents a promising therapeutic strategy with excellent efficacy and translational potential for TNBC.
