Boron carbide nanoparticles for boron neutron capture therapy

Boron agent is widely accepted as one of the most important factors in boron neutron capture therapy (BNCT). In this study, boron carbide (B₄C) nanoparticles were subjected to chemical modification, with the folic acid moiety linked to the surface of the particles by varying the segments of the covalent linker polyethylene glycol (PEG) through γ-aminopropyltriethoxysilane (APTES) functionalization. The resultant products were three boron agents, termed as B₄C-APTES-FA, B₄C-APTES-PEG2K-FA, and B₄C-APTES-PEG5K-FA. A comparison was made between these products and the pristine B₄C nanoparticles by investigating their physicochemical properties and biological performances, including hemolysis, cytotoxicity, and cellular uptake. Subsequently, the modified B₄C-APTES-PEG2K-FA nanoparticles were subjected to <i>in vivo</i> safety assays and biodistribution investigations in mice at various dosages. Upon characterization using ICP-OES, it was found that the boron contents were the highest in the lungs, followed by the liver, spleen, kidneys, hearts, and tumors, and the lowest in the brain and muscles. The boron content in the tumor reached as high as 50 μg per g of dried tissue weight after 24 h of intravenous injection (I.V.), while the tumor-to-muscle and tumor-to-brain ratios of boron contents were found to exceed 3 following 24 hours of intravenous injection. These findings suggest that B₄C nanoparticles are promising for BNCT owing to their high boron content, satisfactory biocompatibility, and abundant chemical modification sites.