Magnetically manipulated and transferrin-modified liposomes for efficient brain delivery of harmine and glioblastoma therapy

Glioblastoma, originating from glial cells in the brain's neuroepithelial tissue, are the most common primary malignant tumors of the central nervous system (CNS). Due to their invasive growth characteristics, most glioblastoma are difficult to completely resect, leaving residual tumor cells that become the source of recurrence. Harmine (HM), an active compound extracted from Peganum harmala L. seeds, exhibits a particularly notable in its anti-glioblastoma activity. However, HM suffers from poor selectivity, low bioavailability, and a tendency to enter the normal brain tissue, where it reversibly and competitively inhibits monoamine oxidase A (MAO-A), leading to neurotoxic side effects such as tremors and convulsions. To improve the therapeutic efficacy and reduce toxicity, this study fabricated a delivery system-based magnetic nanoliposomes (MNLs) formulation modified with transferrin (Tf) on the surface (HM@MNLs-Tf). The high expression of TfR on glioma cells and blood-brain barrier endothelial cells (BMECs) facilitates the efficient crossing of the blood-brain barrier (BBB) and targeting of glioma cells. Additionally, the presence of iron oxide nanoparticles within HM@MNLs-Tf enhances BBB penetration when subjected to an external magnetic field (MF). This mechanism improves the selectivity of HM and reduces the neurotoxicity associated with MAO-A inhibition, thereby increasing its clinical applicability. In vitro and in vivo results demonstrated that the approach employed by this study significantly improved the therapeutic effect of HM to glioblastoma while minimizing its neurotoxicity and side effects.