Phytosomes Loaded with Mastoparan-M Represent a Novel Strategy for Breast Cancer Treatment.

Purpose: Mastoparan-M (Mast-M) has cytotoxic effects on various tumor cells in vitro, including liver cancer and colorectal cancer. However, the anti-tumor mechanism of Mast-M remains unclear and its potential for anti-tumor therapy has not been investigated. Herein, we aimed to develop a novel phytosome formulation loaded with Mast-M and evaluate its efficacy against breast cancer both in vitro and in vivo. Furthermore, we investigated the underlying anti-tumor mechanisms of Mast-M. Methods: The synthesis of Phy-Mast-M involved a co-solvent technique, followed by solvent evaporation. Its anti-tumor mechanism was investigated using CCK-8, clone formation, and apoptosis assays. Subsequently, the biodistribution and anti-tumor efficacy of Phy-Mast-M were assessed in vivo using the 4T1 tumor-bearing mouse model. Finally, the safety of Phy-Mast-M was evaluated in vivo. Results: The prepared Phy-Mast-M demonstrated an exceptional monodisperse size distribution (125.67 ± 45.79 nm), and exhibited excellent stability under different physiological conditions. Phy-Mast-M could inhibit 4T1 cells growth through multiple channels, including arresting cell growth cycle and disturbing mitochondrial membrane integrity. Phy-Mast-M proved significantly higher accumulation at tumor sites in a tumor-bearing mouse model as compared to free Mast-M. Moreover, in vivo anti-tumor studies demonstrated that Phy-Mast-M exhibited superior curative inhibitory effects on tumor growth and favorable biocompatibility. Conclusion: Phy-Mast-M demonstrates significant anti-tumor activity both in vitro and in vivo. Moreover, its potential for clinical translation suggests promising prospects for cancer therapy, offering more drug options for breast cancer patients.