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Ginsenoside Rh2-Based Multifunctional Liposomes for Advanced Breast Cancer Therapy
Chao Hong1,2, Anni Wang1, Jiaxuan Xia1
1Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 201203, People's Republic of China.
Background:
Most solid tumors are not diagnosed and treated until the advanced stage, in which tumors have shaped mature self-protective power, leading to off-target drugs and nanomedicines. In the present studies, we established a more realistic large tumor model to test the antitumor activity of a multifunctional ginsenoside Rh2-based liposome system (Rh2-lipo) on advanced breast cancer.
Methods:
Both cholesterol and PEG were substituted by Rh2 to prepare the Rh2-lipo using ethanol-water system and characterized. The effects of Rh2-lipo on cell uptake, penetration of the tumor spheroid, cytotoxicity assay was investigated with 4T1 breast cancer cells and L929 fibroblast cells. The 4T1 orthotopic-bearing large tumor model was established to study the targeting effect of Rh2-lipo and inhibitory effect of paclitaxel loaded Rh2-lipo (PTX-Rh2-lipo) on advanced breast tumors.
Results:
Rh2-lipo exhibit many advantages that address the limitations of current liposome formulations against large tumors, such as enhanced uptake in TAFs and tumor cells, high targeting and penetration capacity, cytotoxicity against TAFs, normalization of the vessel network, and depletion of stromal collagen. In in vivo study, PTX-Rh2-lipo effectively inhibiting the growth of advanced breast tumors and outperformed most reported PTX formulations, including Lipusu® and Abraxane®.
Conclusion:
Rh2-lipo have improved drug delivery efficiency and antitumor efficacy in advanced breast cancer, which offers a novel promising platform for advanced tumor therapy.
Insights
A novel ginsenoside Rh2-based liposome system (Rh2-lipo) effectively targets and treats advanced breast cancer. This advanced formulation enhances drug delivery and antitumor efficacy, offering a promising new platform for cancer therapy.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Cancer Research
Background:
- Advanced solid tumors possess self-protective mechanisms hindering effective drug delivery.
- Current nanomedicine approaches face limitations in treating large, advanced tumors.
- A realistic large tumor model was developed to evaluate novel therapeutic strategies.
Purpose of the Study:
- To develop and assess a multifunctional ginsenoside Rh2-based liposome system (Rh2-lipo) for advanced breast cancer treatment.
- To investigate the therapeutic potential of Rh2-lipo in a large tumor model.
- To evaluate the efficacy of paclitaxel-loaded Rh2-lipo (PTX-Rh2-lipo) against advanced breast tumors.
Main Methods:
- Rh2-lipo were prepared by substituting cholesterol and PEG with Rh2.
- In vitro studies assessed cell uptake, tumor spheroid penetration, and cytotoxicity using 4T1 breast cancer and L929 fibroblast cells.
- An orthotopic 4T1-bearing large tumor model was used to evaluate in vivo targeting and antitumor effects of PTX-Rh2-lipo.
Main Results:
- Rh2-lipo demonstrated enhanced uptake by tumor-associated fibroblasts (TAFs) and cancer cells.
- The formulation exhibited high targeting and penetration capabilities, with cytotoxicity against TAFs.
- PTX-Rh2-lipo significantly inhibited advanced breast tumor growth, outperforming existing paclitaxel formulations.
Conclusions:
- Rh2-lipo enhances drug delivery efficiency and antitumor efficacy in advanced breast cancer.
- The developed liposome system offers a promising platform for advanced tumor therapy.
- This novel approach addresses limitations of current treatments for large, advanced tumors.
