Objective: The major objective of this study is to develop and evaluate phenyl boronic acid (PBA) conjugated solid lipid nanoparticles (SLNs) (PBA-SUL@SLN) for the targeted delivery of sulindac (SUL) to breast cancer (BC) cells.
Significance: Utilizing a dual approach that combines PBA-mediated targeting with Notch-1 pathway inhibition by SUL, the study aims to enhance therapeutic selectivity and efficacy against an aggressive BC subtype, triple negative BC (TNBC), which lacks well-defined molecular targets.
Methods: The PBA-SUL@SLN formulation was prepared using emulsification-solvent evaporation method and analyzed for the particle size (PS), zeta potential (ZP), entrapment efficiency (EE), and pH sensitive drug release. Cellular uptake studies were conducted to examine selective internalization in TNBC cells. The therapeutic efficacy was assessed by evaluating Notch-1expression modulation of epithelial-to-mesenchymal transition (EMT), cancer stem cell (CSC) activity, and cytotoxic effects in TNBC cell compared to normal cells.
Results: The PBA-SUL@SLN formulation exhibited an optimal PS of (153.35 nm), a ZP of (22.87 mV), and an EE of 83.06%, with preferential drug release observed in the acidic tumor microenvironment. Increased cellular uptake in MDA-MB-231 cells led to notable downregulation of Notch-1, inhibition of EMT, and potential reduction in CSC activity. Cytotoxicity assays revealed strong and selective efficacy against TNBC cells while causing minimal effects on normal cells.
Conclusions: The PBA-SUL@SLN formulation presents a promising targeted therapeutic strategy for TNBC, addressing key limitations of existing treatments.
Keywords: Notch-1 inhibition; Triple-negative breast cancer; phenyl boronic acid; sulindac; targeted drug delivery.