Enhanced boron neutron capture therapy (BNCT) through controlled drug release via boron-loaded nanofiber mats

Boron neutron capture therapy (BNCT) is a novel binary therapy combining boron targeted drugs and neutron irradiation, which can selectively and effectively kill cancer cells at the cellular scale. Controlled release of boron drug and its accumulation in tumor sites are the crux of BNCT. Here, we developed a 10B-boric acid (10BA)-loaded nanofiber applying for BNCT by in situ administration. The nanofibers were obtained by electrospinning technique using polyethylene glycol/polylactide (PEO/PLA) block copolymers. By changing the ratio of hydrophilicity to hydrophobicity of the nanofibers, the controlled release and the effective accumulation of boron 10 isotope (10B) were achieved in situ. The 10B content in tumor could reach to 2540 µg/g, significantly exceeding the required level of 20–50 µg/g for BNCT operation. Utilizing pertinent DNA damage experiments, direct evidence and quantified data of BNCT-induced DNA damage in tumor cells were obtained for the first time. Transcriptome sequencing was employed to predict the molecular mechanisms and potential signaling pathways of BNCT, providing theoretical basis for future combined therapies. The antitumor efficiency of BNCT was demonstrated by establishing mice model of subcutaneous tumor and tumor recurrence. The research presents a novel boron-loaded nanofiber mats for BNCT, which enables controlled drug release and holds significant potential in the treatment of unresectable or postoperative residual tumors.