Dicesium N-succinimidyl 3-(undecahydro-closo-dodecaboranyldithio)propionate, a novel heterobifunctional boronating agent

Abstract

The synthesis of a novel heterobifunctional agent, dicesium N-succinimidyl 3-(undecahydro-closo-dodecaboranyldithio)propionate, is described. This structure contains an active ester component known to react rapidly under very mild conditions with amino groups of proteins, resulting in covalent linkage. With use of this boronating agent, approximately 480 boron atoms have been incorporated per molecule of a polyclonal antibody directed against human thymocytes and 1300 boron atoms per molecule were incorporated into a monoclonal antibody, 17-1A, directed against human colorectal carcinoma cells. Binding of the boronated antibodies to the corresponding target cells was demonstrated by means of membrane immunofluorescence. There was some loss in reactivity, as determined by fluorescent end point titers, but specificity remained unchanged. The data suggest that boronated antibodies potentially could be used to selectively deliver boron-10 to tumor cells in order to achieve their destruction by neutron capture.

Polyhedral Boranes for Medical Applications: Current Status and Perspectives

“…[66] This result indicates that attaching 100 functional groups on the antibody molecule apparently results in the loss of its targeting specificity. It means that minimum modification of the antibody molecule is needed for retention of its immunoreactivity.…”

Polymers and boron neutron capture therapy (BNCT): a potent combination

“…Such an EGPR can therefore be used as a target, using EGF bioconjugates to deliver boron atoms to cancer cells. Barth and coworkers developed several methodologies to boronate EGF, 32 such as using the thiol-maleimide "click" chemistry reaction. Starburst dendrimers composed of repetitive polyamidoamino (PAMAM) groups were functionalised on their terminal amine groups by an isocyanato polyhedral borane and further functionalised with a thiol group to react with the maleimide groups of EGF derivatives (Fig.…”

Synthesis and Characterization of Carborane Functionalized Dendronized Polymers as Potential Boron Neutron Capture Therapy Agents

“…Therefore, it is theoretically possible to destroy tumor cells without affecting adjacent healthy cells if a sufficiently high 10 B concentration is selectively delivered to the tumor cells. This poses a major challenge to BNCT, as it has been difficult to achieve selective delivery of adequate concentrations of ,0 B, a minimum of 10 9 10 B atoms per cell or approximately 30 jag 10 B per gram of tumor tissue (5,6). One of the most effective ways to address this issue is to incorporate a high number of B atoms within drug delivery vehicles (7).…”