Repurposing luteolin through nanotechnology for triple-negative breast cancer management

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with limited therapeutic options and a poor prognosis. Luteolin, a naturally occurring flavonoid, exhibits potent anticancer activity by inhibiting cell proliferation, migration, invasion, angiogenesis, and metastasis while inducing apoptosis and other forms of programmed cell death through modulation of multiple signaling pathways. However, its clinical application is restricted by poor aqueous solubility, low oral bioavailability, extensive first-pass metabolism, and rapid systemic elimination. Nanotechnology-based delivery systems, including liposomes, polymeric nanoparticles, solid lipid nanoparticles, and nanostructured lipid carriers, have emerged as promising strategies to overcome these limitations by enhancing solubility, stability, bioavailability, tumor targeting, and therapeutic efficacy. This review summarizes the structure–activity relationship, anticancer mechanisms, pharmacokinetic challenges, and recent advances in nano-luteolin formulations for TNBC management, highlighting future opportunities for clinical translation.