Molecular effects of paclitaxel-elacridar nanoemulsions in breast cancer cells: impact on uptake, cell cycle and signaling pathways

In this study, we investigated how paclitaxel incorporation in a bioadhesive, hyaluronic acid-modified nanoemulsion (NE) containing the P-glycoprotein inhibitor elacridar influenced its molecular effects and mechanism of action in breast cancer cells. Incorporation of paclitaxel with elacridar in the nanoemulsion resulted in a 2.5-fold increase in cellular uptake compared to the drug solution. Clathrin-mediated endocytosis contributed to nanoemulsion-mediated cell internalization, with both paclitaxel and NBD-phosphatidylcholine (nanoemulsion surfactant) partially co-localizing with transferrin. The nanoemulsion amplified paclitaxel-mediated chromatin condensation and expression of proteins involved in apoptosis, with a 2.5-fold increase in PARP1 (Poly (ADP-ribose) polymerase 1) cleavage and a 1.7-fold downregulation of BCL2 (B-cell lymphoma protein 2) expression. Apoptosis was maintained as the main mechanism of cell death. The formulation also reduced cell migration (3-fold) compared to the solution at concentrations lower than IC₅₀, while the clonogenic effect (17-fold) was not hindered, supporting a broader impact on tumorigenesis.