SELECTIVE BORON DRUG-DELIVERY TO BRAIN-TUMORS FOR BORON NEUTRON-CAPTURE THERAPY

Malignant glioma is one of the most deadly forms of cancer in humans a nd remains refractory to presently available treatments. Boron neutron capture therapy (BNCT) is a promising therapeutic modality for the tr eatment of malignant brain tumors. For successful BNCT, a sufficient q uantity of boron atoms must be selectively delivered to individual bra in tumor cells while at the same time the boron concentration in the n ormal brain tissue should be kept low to minimize the damage to normal brain tissue. However, the brain entry of drugs is restricted by the blood-brain barrier (BBB), even though the permeability of the patholo gical area of this barrier may be partially increased due to the prese nt of brain tumors. Therefore, selective delivery of boron to tumor ce lls across the BBB is a major challenge to the BNCT of brain tumors. T his review briefly discusses four main mechanisms responsible for drug transport across the BBB. Brain tumor-localizing boron compounds are described, such as borocaptate sodium, p-boronophenylalanine, boronate d porphyrins and boronated nucleosides. Strategies employed to selecti vely deliver boron drug into brain tumors are reviewed including hyper osmotic BBB modification, biochemical opening of BBB, electropermeabil ization and direct intracerebral delivery of boron drugs. Conjugation of boron drugs to macromolecules like monoclonal antibodies and epider mal growth factor are discussed for active tumor targeting. Boron deli very via microparticles such as liposomes, high density lipoproteins a nd nanoparticles is also covered for their potential utilization in BN CT of brain tumors. (C) 1997 Elsevier Science B.V.