TPGS Nano Formulation in Triple Negative Breast Cancer

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer lacking estrogen receptors, progesterone receptors, and HER2 expression, which limits targeted therapeutic options and contributes to poor clinical outcomes. D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS), a water-soluble derivative of natural vitamin E, has emerged as a promising nanocarrier due to its amphiphilic nature, ability to enhance drug solubility, inhibit P-glycoprotein (P-gp), and selectively induce apoptosis in cancer cells. This review explores the physicochemical and pharmacological properties of TPGS and its application as a nanocarrier in TNBC therapy. TPGS induces cytotoxic effects via multiple mechanisms, including P-gp inhibition, reactive oxygen species (ROS) generation, mitochondrial dysfunction, and DNA damage, leading to caspase-dependent and independent cell death. It also enhances the therapeutic efficacy of chemotherapeutic agents by overcoming multidrug resistance. Furthermore, the paper discusses the molecular heterogeneity and complex signaling pathways involved in TNBC pathogenesis—such as PI3K/AKT/mTOR, Notch, Wnt/β-catenin, and Hedgehog—which offer potential targets for combinatory or synergistic treatment strategies involving TPGS-based nanoformulations. These findings support the role of TPGS as a multifunctional excipient and therapeutic agent in addressing the challenges associated with TNBC treatment.