Targeted Boron Neutron Capture Therapy Using Polymalic Acid Derived Nano-Boron to Treat Glioblastoma.

Despite extensive efforts, glioblastoma multiforme (GBM), the most malignant brain cancer, continues to pose significant challenges to effective treatment, with limited progress in patient survival over the last three decades. This study addresses shortcomings of conventional therapies, particularly radiotherapy (RT), which faces limitations due to radio-resistance and toxic radiation doses. Boron neutron capture therapy (BNCT) is a promising alternative, delivering targeted radiation to tumor cells with minimal damage to healthy tissue. However, the key challenge lies in achieving sufficient boron uptake selectively in tumor cells. We have developed a novel nanomedicine-based approach, utilizing polymalic acid (PMLA) as a delivery vehicle, carrying multiple boron-10 molecules per nanoconjugate to increase the intracellular concentration of boron-10 for effective boron neutron capture therapy. Our novel nanodrug (Nano-Boron) incorporates isotopically enriched 4-boronophenylalanine (BPA) as a source of boron-10 and Angiopep-2 (AP2) peptide for blood-brain barrier penetration and tumor targeting. The PMLA platform allows for the attachment of a large quantity of boron-10, enhancing the intracellular boron concentration and, consequently, the efficacy of BNCT. This innovative approach holds the potential to address the unmet clinical need in GBM treatment and improve patient survival and quality of life.