Antibody-Based Receptor Targeting Using an Fc-Binding Peptide-Dodecaborate Conjugate and Macropinocytosis Induction for Boron Neutron Capture Therapy

[Image: see text] Boron neutron capture therapy (BNCT) is a radiation method used for cancer therapy. Cellular uptake of boron-10 ((10)B) atoms induces cancer cell death by the generation of alpha particles and recoiling lithium-7 ((7)Li) nuclei when the cells are irradiated with low-energy thermal neutrons. Current BNCT technology shows effective therapeutic benefits in refractory cancers such as brain tumors and head and neck cancers. However, improvements to cancer targeting and the cellular uptake efficacy of the boron compounds and the expansion of the diseases treatable by BNCT are highly desirable. In this research, we aimed to develop an antibody-based drug delivery method for BNCT through the use of the Z33 peptide, which shows specific recognition of and interaction with the Fc domain of human IgG, for on-demand receptor targeting. In addition, we determined with an in vitro assay that macropinocytosis induction during antibody-based drug delivery is crucial for the biological activity of BNCT.