Synthesis of Carborane Derivatives of Cholesterol for Incorporation into Unilamellar Liposomes and Evaluation as Potential Agents for Boron Neutron Capture Therapy
Tate, Colby Clay
Boron neutron capture therapy, or BNCT, is a binary cancer therapy based on the ability of the boron-10 isotope to capture thermal neutrons. The neutron capture reaction is the formation of a highly energetic boron-11 atom. The boron-11 atom fissions, producing both a lithium atom and an alpha particle. Along with the two products mentioned, a significant amount of energy is produced. The energy is dissipated within a distance of approximately 10 pm in tissue or roughly the size of a single eukaryotic cell. Hence, if a large enough concentration of boron-10 atoms can be selectively localized in the tumor cell, irradiation of the cell would result in the destruction of the tumor cell while leaving surrounding, normal tissue unaffected. The major limitation of BNCT is the production of boron-containing compounds that will selectively localize in the tumor cell with large enough concentrations to be effective. In 1999, a series of carborane-containing derivatives of cholesterol, containing a six carbon-atom tether between the carborane and the cholesterol moieties, was prepared. Although the attempt was made to incorporate some of the compounds into the hydrophobic bilayer of unilamellar liposomes, the compounds that were incorporated did not contain sufficient boron for the biodistribution experiments. Additionally, the synthetic schemes were somewhat cumbersome, yields were relatively low, and problems with the reported syntheses were noted. Therefore, a shorter synthetic route would enhance the ability to prepare the compounds in a given period of time and also increase the overall yield. Additionally, the length of the alkyl chain tether should affect the ability of the carborane derivatives to pack into the bilayer of the liposomes. Therefore, the goal of this research project is the design of an improved synthetic scheme and the preparation of new carborane derivatives of cholesterol, with varying tether lengths, for incorporation into unilamellar liposomes. New synthetic routes have been developed for the cholesterol derivatives and eight new compounds have been prepared.
boron-neutron capture therapy, cancer treatment, boron compounds, cholesterol, liposomes
Tate, C. C. (2002). Synthesis of carborane derivatives of cholesterol for incorporation into unilamellar liposomes and evaluation as potential agents for boron neutron capture therapy (Unpublished thesis). Southwest Texas State University, San Marcos, Texas.