Methotrexate-modified docetaxel liposome targeting with ginsenoside Rh2 as a membrane stabilizer for the treatment of ovarian cancer

Abstract

At present, nano-agent-targeted therapy has become the main means of clinical treatment for ovarian cancer. Conventional liposomes, while commonly used as drug carriers, often suffer from stability issues that reduce drug bioavailability. Cholesterol, a frequent component in liposome membranes, may cause adverse effects such as dyspnea and shortness of breath when accumulated excessively. To address these challenges, we employed G-Rh2 as an alternative to cholesterol in liposome membranes as it acts as a membrane stabilizer to increase the stability of the liposome system. We prepared methotrexate-modified docetaxel liposomes (MTX@DTX-Rh2-Lips), characterized their properties and evaluated their stability. The ability of MTX@DTX-Rh2-Lips to target SKOV3 cells and loaded mice was confirmed. Assessments through CCK-8, EDU proliferation, and wound healing assay demonstrated the in vitro antitumor effects of MTX@DTX-Rh2-Lips. The in vivo antitumor effects of MTX@DTX-Rh2-Lips were evaluated by immunohistochemistry and immunofluorescence staining. Our findings revealed that MTX@DTX-Rh2-Lips was uniformly spherical and stable, effectively targeting the tumor site, inhibiting the proliferation, invasion, metastasis, and angiogenesis of SKOV3 cells, and affecting the expression of tumor-associated proteins, with a good safety profile. In conclusion, the successful establishment of MTX@DTX-Rh2-Lips introduces promising avenues for the clinical treatment of ovarian cancer.