Elemental Boron Nanoparticles for Boron-Neutron Capture Therapy of BT-474 Human Breast Cancer

Breast cancer remains one of the most common malignancies worldwide. Highly invasive HER2-positive breast cancer carries a high risk of metastasis and poses a significant therapeutic challenge. Boron neutron capture therapy (BNCT) may be an option for patients with this severe diagnosis. Here we evaluated the effectiveness of BNCT with elemental boron nanoparticles obtained by laser fragmentation and coated Silane-PEG-COOH and conjugated with the Affibody _ZHER2:342 guide protein (BPs) against the HER2-positive breast cancer. The MTT assay after BNCT with BPs revealed an almost twofold reduction in surviving BT-474 tumor cells compared to the control group. The results of the clonogenic test showed totally death of BT-474 cells after BNCT with BPs at a concentration of 40 μg/mL in the culture medium. The same results was found for in vivo. In female SCID mice bearing BT-474 breast tumor xenografts, BNCT with intratumoral injection of BPs at a dose of 60 mg/kg led to a significant slowdown in xenograft growth beginning on the 17th day compared with control animals and the 39th day compared with irradiated females. A single intratumoral administration of BPs at a dose of 60 mg/kg did not show toxic effects. Histological examinations did not reveal systemic accumulation of the studied BPs in major organs; instead BPs was selectively retained within the xenografts and surrounding tissues. Thus, laser fragmented functionalized with Silane-PEG-COOH and the Affibody _ZHER2:342 (BPs B-PEG-AFF) represent a promising platform for boron delivery in targeted BNCT applications.