Investigation of the Reactivity of Three Polyhedral Borane Anions with Albumins
Date
2003-08
Authors
McVey, William Jefferson
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Abstract
Boron neutron capture therapy (BNCT) has been proposed as a potential improvement on existing clinical modalities in the treatment of aggressive brain tumors, such as gliobastoma multiforme, and metastatic melanoma. Theoretically, BNCT is an ideal binary therapy in which each component is non-lethal. Boron-10 atoms, located in the tumor, react with thermal neutrons to produce an alpha particle and a lithium-7 particle. The energy produced by the reaction dissipates in a distance of approximately 8-10 pm in tissue.1 The application of BNCT is dependant on the site specific delivery, and retention, of high concentrations of boron-containing compounds to the tumor.
Unilamellar liposomes have permitted the selective delivery of water soluble, polyhedral borane anions that have no inherent tumor specificity.2-4 Murine biodistribution studies have established the retention of certain polyhedral borane anions within the tumor; however, the chemical nature of the retention has not been aiscertained.2-4 Researchers have proposed that certain polyhedral borane anions will react with nucleophilic sites on proteins or, in the case of a boron-containing compound which possesses a thiol substituent, form a disulfide bond. Although this hypothesis has been used for the design of new compounds, there has been no research to date to support the hypothesized formation of a covalent bond by any of the proposed mechanisms.
Three polyhedral borane anions were selected for evaluation based on their in vivo murine biodistributions. The compounds were allowed to react with serum albumins and the products of the reaction were evaluated by gel electrophoresis, matrix assisted laser desorption mass spectroscopy (MALDI-MS), UV-Vis spectroscopy, and HPLC.
Additionally, a well established protocol using DTNB provided a significant indication of disulfide bond formation between a polyhedral borane anion possessing a thiol substituent and bovine serum albumin.5 The results indicate that complexes are formed between the albumins and at least two of the polyhedral borane anions. The protein boron complexes are highly resistant to disruption, leading to the conclusion that a covalent bond, while not certain, is a possibility. Further testing of the existing complexes will be necessary to confirm the formation of a covalent bond and to locate the binding sites.
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Keywords
boranes, capture therapy, boron-neutron, serum albumin, cancer, treatments
Citation
McVey, W. J. (2003). Investigation of the reactivity of three polyhedral borane anions with albumins (Unpublished thesis). Southwest Texas State University, San Marcos, Texas.