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).

Keywords: (10)B-boron phosphate; (10)B-containing nanoparticles; Anti-EGFR antibody; Boron neutron capture therapy; H&N tumors; Microwave arcing method.