Simple Cytosolic and Nuclear Introduction of Boron Compounds Using Cationic Lipids to Enhance Cancer Cell-Killing Activity in Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT), a type of nuclear capture-based radiotherapy, has received extensive attention because of its strong anticancer effects, especially in head and neck cancers. This therapy was approved for clinical use in 2020 in Japan. This study demonstrated a technique that effectively uses the electrostatic interactions of negatively charged borane cage (polyhedral borane anion) of disodium mercaptoundecahydro-closo-dodecaborate (BSH) and positively charged cationic lipids or arginine-rich cell-penetrating peptides as carriers to enhance the efficiency of cellular uptake. Mixing of fluorescein isothiocyanate (FITC)-labeled BSH (FITC-BSH) with the cationic lipids led to increased cytosolic release and nuclear accumulation of FITC-BSH, resulting in superior cancer cell-killing activity following thermal neutron irradiation. This simple technique and our experimental results provide essential insights for the further development of BNCT.