Recent Advances in Surface-Engineered Polymeric Nanoparticles for Targeted Paclitaxel Delivery in Breast Cancer Therapy.

Breast cancer remains a leading cause of cancer-related mortality worldwide. Paclitaxel (PTX), a first-line chemotherapeutic agent widely used in breast cancer, is widely used due to its potent mechanism of action against rapidly dividing cancer cells. However, its clinical application is significantly hindered by poor solubility, systemic toxicity, and associated adverse effects. Encapsulating PTX in polymeric nanoparticles presents a promising strategy to overcome these limitations by extending drug release, enhancing drug's bioavailability, and enabling active targeting. This review uniquely focuses on recent advances in surface-functionalized polymeric nanoparticles specifically engineered for targeted delivery of PTX in breast cancer therapy and consolidates their translational relevance and next-generation design considerations. Unlike general reviews on polymeric nanocarriers, this article specifically focuses on ligand-functionalized polymeric nanoparticles designed for active targeting of breast cancer cells, integrating biological rationale, receptor specificity, and translational relevance. Surface-engineered polymeric nanoparticles functionalized with ligands such as folic acid, hyaluronic acid, aptamers, and peptides can specifically target overexpressed receptors on cancer cells, including CD44, HER2, and folate receptors. These ligand-receptor interactions facilitate receptor-mediated endocytosis, enhancing intracellular drug delivery while minimizing systemic toxicity. The review highlights key design considerations, including ligand density, nanoparticle architecture, and multifunctionality of next-generation PTX nanocarriers. The development of PTX-loaded polymeric nanoparticles with surface modifications represents a significant advancement in precision drug delivery for breast cancer, addressing key treatment challenges and paving the way for clinical translation.