Advancements in Lipid Nanotechnology for the Treatment of Triple-Negative Breast Cancer: Mechanistic Insights and Future Prospects

The high resistance to therapy, molecular heterogeneity, early metastasis, and quick drug resistance make triple-negative breast cancer (TNBC) difficult and even impossible to treat. The conventional chemotherapy is highly toxic, not specifically targeting the tumor, and has limited efficacy, so more sophisticated delivery mechanisms are required. To overcome these shortcomings, lipid nanotechnology is provided as a controlled, targeted, and multifunctional drug delivery system. This review outlines the recent developments of lipid nanoparticles for TNBC, including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, lipidpolymer hybrids, ionizable lipid nanoparticles, and biomimetic vesicles. These systems enable improved tumor targeting and delivery of chemotherapeutics, gene editing agents, and combination therapeutics. Rational design, targeting strategies, modulation of the tumor microenvironment, targeting cancer stem cells, and breaking multidrug resistance are highlighted. Pharmacokinetic, safety, manufacturing, regulatory, and translational issues are discussed, along with pre-clinical and emerging clinical evidence. Lastly, future directions are suggested to help develop modular, precise, and clinically scalable lipid nanoparticle systems for effective management of TNBC.