Ginsenoside Rh2-Based Multifunctional Liposomes for Advanced Breast Cancer Therapy

Abstract

Chao Hong,1,2,* Anni Wang,1,* Jiaxuan Xia,1 Jianming Liang,1,3 Ying Zhu,1 Dan Wang,1,4 Huaxing Zhan,4 Chunbo Feng,5 Xinnan Jiang,5 Junjie Pan,6 Jianxin Wang1,7 1Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 201203, People’s Republic of China; 2School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 4Xiamen Ginposome Pharmaceutical Co., Ltd, Xiamen, 361026, People’s Republic of China; 5R&D Center, Shanghai Jahwa United Co., Ltd, Shanghai, 200082, People’s Republic of China; 6Department of Cardiology, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 7Institute of Integrated Chinese and Western Medicine, Fudan University, Shanghai, 200040, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junjie Pan; Jianxin Wang, Email [email protected]; [email protected]: 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. Keywords: nanomedicine, tumor microenvironment, chemotherapy, tumor-associated fibroblast

Keywords

• nanomedicine
• tumor microenvironment
• chemotherapy
• tumor-associated fibroblast