One step synthesis of 10B-enriched 10BPO4 nanoparticles for effective boron neutron capture therapeutic treatment of recurrent head-and-neck tumor

Abstract

Recurrent head-and-neck (H&N) cancer is one of the most malignant cancers in the world. Various treatment modalities, such as radiation therapy, chemotherapy, and surgery were adopted to treat H&N cancer, but recurrence of H&N tumor always occurs again, leading to poor prognosis and low 5-year survival rate. Recently, boron neutron capture therapy (BNCT) emerges an alternative modality for curing recurrent tumors. Presently, boron phenylalanine-fructose (BPA-F) and sodium borocaptate (BSH) are the two best BNCT molecular drugs, which, however, have poor therapeutic efficacies and are lack of tumor-targeting ability. In this study, 10B-riched (98.5% 10B) boron phosphate nanoparticles (10BPO4 NPs) of ∼100 nm in size were prepared in a single step using a unique microwave arcing method. The 10B-enriched 10BPO4 NPs were surface-modified with anti-EGFR antibody to endow the targeting ability toward H&N cancer cells. In in-vivo xenograft mice model, a large amount (∼63 μg 10B/g cancer cells) of 10B atoms could be effectively accumulated at the H&N tumor sites using 10BPO4 NPs as BNCT reagents. In in-vitro neutron irradiation experiments, 72% cell deaths were observed from anti-EGFR-10BPO4 NPs-treated H&N cancer cells, which is ∼2.4 folds higher than that (30%) treated with the most effective molecular drug, BPA-F. We demonstrated that upon neutron irradiation, the anti-EGFR-10BPO4 NPs could exert a much higher extent of destruction of H&N tumor, as well as effective suppression of the probability of H&N tumor recurrence, as compared to the most effective molecular drug, BPA-F. The median survival of the BNCT treated mice with anti-EGFR-10BPO4 NPs extends beyond 75 days, which is far better than the mice treated with BPA-F (33 days), blank + NR mice (25), and blank mice (23 days).