The Role of Chemistry in the Development of Boron Neutron Capture Therapy of Cancer

Abstract

A therapeutic method that selectively destroys malignant cells in the presence of normal cells is a highly valued goal of oncologists and the possible salvation of cancer patients afflicted with some incurable forms of the disease. Selective cell destruction is, in principle, possible with a binary therapeutic strategy based upon the neutron capture reaction observed with the 10B nucleus and a neutron of low kinetic energy (thermal neutron). This nuclear fission reaction produces both 4He and 7Li+ nuclei along with about 2.4 MeV of kinetic energy and weak γ‐radiation. Since the energetic and cytotoxic product ions travel only about one cell diameter in tissue one may specify the cell type to be destroyed by placing innocent 10B nuclei on or within only the doomed cells. This article describes the current status of chemical research aimed at the eventual adoption of this therapeutic method (boron neutron capture therapy or BNCT). The multidisciplinary nature of this research effort involves chemistry, biology, nuclear physics, medicine, and related specialties. Methods devised for bringing 10B nuclei to tumor cells in therapeutic amounts are correlated with the structure of a generalized cell and the various cellular compartments available for boron localization. The synthesis methods employed for the creation of boron‐containing biomolecules and drugs are presented along with representative data concerning their efficacy in tumor localization. The outlook for BNCT is especially bright at this time because of rapid developments in the fields of bioorganometallic chemistry, microbiology, immunology, and nuclear science, to name but a few. Very effective boron delivery vehicles have been demonstrated, and through the interaction of chemistry and biology these species are undergoing further improvement and evaluation of their suitability for BNCT.

Boron neutron capture therapy demonstrated in mice bearing EMT6 tumors following selective delivery of boron by rationally designed liposomes

“…For BNCT to be successful in the treatment of cancer, the following criteria must be completely addressed: (i) preferential or selective uptake of 10 B-containing agent(s) by tumor tissue, relative to normal tissue, at concentrations sufficiently high to deliver a therapeutic dose of 10 B atoms (≥20 μg B in tumor tissue with rapid clearance from blood and normal tissues; and (iii) low systemic toxicity of all 10 B delivery agents (1)(2)(3)(4)(5)(6)(7). Practically speaking, the 10 B agents used should not be excessively difficult or costprohibitive to prepare, and their synthesis should occur in high yield from readily available starting materials and be amenable to scale up.…”

Polyester Dendrimers: Smart Carriers for Drug Delivery

“…The use of other non-radioactive isotopes such as gadolinium has been limited, and to date, it has not been used clinically. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of malignant brain tumors and recurrent head and neck cancers [158][159][160][161]. Consequently, efficient methods for the delivery of boron-10 to biological tissues have been the subject of longstanding research.…”

“…However, an obstacle to mainstream application of BNCT for cancer treatment has been the selective delivery of adequate boron concentrations to target tissues [162]. To address this problem, high boron content species such as polyhedral borane clusters, closo-[B 10 [158]. With this in mind, Adronov and coworkers prepared aliphatic polyester dendrimers based on bis-HMPA that incorporate an easily controllable number of carboranes within the interior of the dendritic structure [163].…”

Clusters: A bridge across the disciplines of environment, materials science, and biology

“…Recently, new generations of boron compounds have been designed to achieve higher tumor cell selectivity than the previous BNCT agents. Boron containing amino acids, related peptides, porphyrins, DNA binders, and other tumor-targeting anchor agents are being attached to a polyhedral borane skeleton for better tumor-cell recognition (75,76).…”