Synthesis of boron-containing dendritic molecules and polymer-silica hybrid nanoparticles for neutron capture therapy of cancer.

摘要

This thesis describes the synthesis and properties of boron-containing compounds intended for use in Neutron Capture Therapy of Cancer, a binary form of treatment based on the cytotoxic radiation, which arises after capture of a thermal neutron by a boron-10 nuclide and the resulting fission reaction. The success of this therapy is based on the delivery of large numbers of boron atoms to cancerous cells in a selective fashion. Dendritic and nanoparticle-based boron-carriers are the best candidates to meet these requirements.;An alternative approach involves the design of small silica spheres and their use to initiate the growth of various polymers that possess functionalizable side chains. These reactive centers are then coupled with carborane-containing moieties, resulting in polymer-silica hybrid nanoparticles approximately one hundred nanometers in size and carrying a very large boron-payload (several hundreds of thousands of boron atoms). In addition, these nanoparticles can also be made fluorescent by introducing a layer of dye within their core.;Several of the boron-containing dendritic constructs are currently being used in primary biological evaluations while it is envisioned that fluorescent silica nanoparticles carrying heavy boron payloads in the form of boron-containing polymers and capable of targeting the neovasculature of growing tumors will perform astonishingly in neutron capture therapy applications.;Thus, this study initially focuses on the preparation of molecular constructs that can be described as resulting from the coupling of neutral polyhedral carboranes containing ten boron atoms with dendritic compounds of various chemical composition and size, such as generation-1 polyester- and polyamide-based dendrons and generation-2 polyesters. These compounds are designed to be biocompatible contain up to 60 boron atoms and retain a reactive center that will allow their incorporation into more complex structures.