Dual-Functional Nanoliposome with High BPA Loading for Targeted MRI-Guided BNCT of Glioblastoma.

Glioblastoma is a highly malignant brain tumor with few available therapeutic options, for which boron neutron capture therapy (BNCT) has emerged as a promising precision radiotherapy approach. However, its efficacy remains suboptimal due to inadequate tumor targeting of boron agents and lack of in vivo visualization. Herein, a gadolinium-boron integrated lipid nanocarrier (BPA-F&DOTA-Gd@LIPO-ANG) was developed for targeted boron delivery and MRI-guided BNCT. BPA-F and DOTA-Gd were coloaded into lipid nanocarriers using a microfluidic system, with Angiopep-2 modification to enhance blood-brain barrier penetration and glioma targeting. Following cellular uptake, BPA-F&DOTA-Gd@LIPO-ANG effectively increased boron accumulation in glioma cells, inducing significant apoptosis and DNA damage upon neutron irradiation. Intravenously injected into orthotopic glioma model mice, BPA-F&DOTA-Gd@LIPO-ANG selectively accumulated in the tumor site, increasing tumor-to-normal tissue (T/N) and tumor-to-blood (T/B) ratios. Enhanced boron accumulation facilitated greater cytotoxic effects mediated by high-energy rays from the boron capture reaction, leading to significantly prolonged mice survival. In addition, in vitro and in vivo MRI validations confirmed its MRI visualization capability, meeting the demand for boron drug imaging for BNCT diagnosis and treatment integration. Overall, these results suggest that BPA-F&DOTA-Gd@LIPO-ANG is a promising targeted boron delivery system for MRI-guided BNCT in glioblastoma treatment.