Ligand-functionalized nanocarriers for targeted breast cancer therapy: advances in receptor-mediated drug delivery

Breast cancer remains one of the most common malignancies found in women worldwide, with treatment outcomes often limited by nonspecific pharmacokinetics, systemic toxicity, and intratumoral heterogeneity. This review synthesizes recent advances in ligand–receptor–mediated nanocarrier systems explored for breast cancer drug delivery. First, it discusses the molecular diversity of breast cancer subtypes and highlights a number of commonly investigated targets, including HER2, CD44, estrogen receptors, folate receptor, and transferrin receptor, with particular emphasis on their relevance to receptor-mediated uptake. Ligand-functionalized nanocarriers have demonstrated improved receptor-specific binding and cellular internalization in preclinical models, potentially enabling enhanced intratumoral drug exposure while limiting off-target interactions. A wide range of ligands, including monoclonal antibodies, peptides, aptamers, and small molecules such as folic acid, is being investigated to facilitate site-specific delivery and to overcome mechanisms associated with multidrug resistance. Furthermore, dual- and multi-ligand designs and stimuli-responsive platforms are being developed to address intratumoral heterogeneity and achieve controlled payload release. Overall, ligand-directed nanocarrier systems represent a promising approach; however, the majority of platforms remain in preclinical development or early-stage clinical testing. Additional effort is needed to establish clinical benefit, enable scaleable manufacturing, and harmonize safety and regulatory considerations. Future directions include refinement of translational study design and integration of theranostic capabilities to support treatment monitoring.