Lactoferrin and Nanotechnology: New Insights Into Glioblastoma Therapy.

AIM: This review aimed to explore emerging therapeutic strategies for glioblastoma multiforme (GBM) through the integration of lactoferrin (LF) and nanotechnology, emphasizing mechanisms that improve drug delivery across the blood-brain barrier (BBB). METHODS: Published studies on LF-based nanocarriers and their biological mechanisms were systematically reviewed, focusing on LF's molecular interactions, tumor-targeting capacity, and the design of nanoscale delivery systems capable of enhancing drug bioavailability and selectivity. RESULTS: LF, an iron-binding glycoprotein with antimicrobial, antioxidant, and antitumor properties, can interact with low-density lipoprotein receptor-related protein-1 (LRP1), enabling its transport across the BBB and preferential uptake by glioblastoma cells. Nanocarrier systems incorporating LF improved the solubility, circulation half-life (typically 2- to 5-fold enhancement compared with free drug), and therapeutic performance of chemotherapeutic agents while minimizing systemic toxicity. Studies demonstrated that LF-based nanoparticles could induce apoptosis, inhibit tumor growth (with tumor volume reductions ranging from approximately 40% to 70% in orthotopic GBM models), and enhance radiosensitivity in GBM models. CONCLUSION: LF provides a promising molecular platform for targeted glioblastoma therapy. When integrated with nanocarrier technologies, it enhances therapeutic efficacy, stability, and safety of anticancer agents. The combined LF-nanocarrier approach represents a rational and innovative strategy for improving treatment outcomes in glioblastoma multiforme.