A pioneer review on lactoferrin as versatile macromolecular ligand for targeting cancer: recent advances

This review critically evaluates the emerging role of lactoferrin, an iron-chelating glycoprotein, as a macromolecular ligand in precision cancer therapy. Lactoferrin exhibits potent anti-tumour, anti-inflammatory, and immunomodulatory properties and targets cancer cells via high-affinity binding to transferrin and LDL receptor-related proteins, enhancing selectivity and minimizing off-target toxicity. It modulates key oncogenic pathways such as PI3K/Akt and MAPK to suppress tumour growth and metastasis. Nanoformulations-like liposomes and polymeric nanoparticles-improve pharmacokinetics, enable targeted drug delivery, and enhance therapeutic efficacy. Lactoferrin's ability to cross biological barriers, including the blood-brain barrier via receptor-mediated transcytosis, offers promise for treating difficult cancers such as glioblastoma. Additionally, it enhances anti-tumour immunity by activating NK cells and polarizing macrophages to the M1 phenotype. Importantly, lactoferrin helps overcome multidrug resistance by modulating efflux pumps like P-glycoprotein. Integrating molecular insights with preclinical and clinical evidence, this review underscores lactoferrin's transformative potential in precision oncology through advanced nanoformulations and synergistic immunomodulatory mechanisms.