Application of drug delivery system to boron neutron capture therapy for cancer

Background: Tumor cell destruction in boron neutron capture therapy (BNCT) is due to the nuclear reaction between 1013 and thermal neutrons (B-10 + (1)n -> Li-7 + He-4 (alpha) + 2.31 MeV (93.7 %)/2.79 MeV (6.3 %)). The resulting lithium ions and alpha particles are high linear energy transfer (LET) particles which give a high biological effect. Their short range in tissue (5-9 mu m) restricts radiation damage to those cells in which boron atoms are located at the time of neutron irradiation. BNCT has been applied clinically for the treatment of malignant brain tumors, malignant melanoma, head and neck cancer and hepatoma. Sodium mercaptoundecahydro-dodecaborate ((Na2B12H11SH)-B-10: BSH) and borono-phenylalanine ((10)BPA) are currently being used in clinical treatments. These low molecule compounds are easily cleared from cancer cells and blood, so high accumulation and selective delivery of boron compounds into tumor tissues and cancer cells are most important to achieve effective BNCT and to avoid damage to adjacent healthy cells. Objective: In order to achieve the selective delivery of boron atoms to cancer cells, a drug delivery system (DIDS) is an attractive intelligent technology for targeting and controlled release of drugs. Methods: We performed literature searches related to boron delivery systems in vitro and in vivo Results: We describe several DDS technologies for boron delivery to cancer tissues and cancer cells from the past to current status. We are convinced that it will be possible to use liposomes, monoclonal antibodies and WOW emulsions as boron delivery systems for BNCT clinically in accordance with the preparation of good commercial product (GCP) grade materials.