Boron-delivery agents

Several dendrimeric borane and carborane systems have been developed for use as boron-delivery agents.147 In vitro tests with a boronated dendrimer-epidermal growth factor bioconjugates indicated that they are endocytosed, resulting in the accumulation of boron in lysosomes. 

Synthesis of the first fully characterized, water-soluble boronated phthalocyanine was reported by Kahl and Li (1996). The product contained 40 boron atoms per molecule (27 wt% B) and may be useful as a tumor-seeking boron delivery agent for BNCT. Then, it was synthesized with two tetra-substituted zinc(II) phthalocyanines carrying 4 carbon-carbon linked o-carboranyl-units again with 40 boron atoms (27.5 wt% B) (Giuntini et al. 2005). An in vitro model test encourages their evaluation as possible BNCT photosensitizers. 

The polyhedral borane ion [n-B2oH,8] reacts with liquid ammonia in the presence of a suitable base to produce an apical-equatorial isomer of the [B2oH,7NH3] ion. This species undergoes acid-catalyzed rearrangement to an apical-apical isomer. The sodium salts of both isomers were encapsulated in unilamellar liposomes, composed of distearoyl phosphatidylcholine/cholesterol, and investigated as boron delivery agents for BNCT (Feakes et al. 1994 Shelly et al. 1992). 

The determination of tumor °B levels is required for accurate neutron dosimetry during BNCT. It is mandatory in order to predict the efficacy of boronated compounds for BNCT. Thus, BNCT requires study of the biodistribution of boron delivery agents used. It is clear that the direct physical detection of boron by nondestructive methods is preferable. 

The first section consists of three chapters covering the medical uses of boron. Chapter 1 by Lesnikowski describes some of the properties of boron clusters that are important for medical applications and presents some examples of boron clusters in different types of medical applications. The following two chapters describe bioactivity of two specific types of boron compounds carbaboranyl phosphonates (in Chapter 2 by Stadlbauer and Hey-Hawkins) and metal bis(dicarbollides) (Chapter 3 by Konvalinka et al). The former compounds are active as pesticides, bactericides and gameticides, while the later are useful as inhibitors of HIV protease. Both classes have been studied as boron delivery agents for boron neutron capture therapy in cancer treatment. 

Byun, Y. Thirumamagal, B. T. S. Yang, W. L. Eriksson, S. Barth, R. F. Tjarks, W. Preparation and biological evaluation of B-lO-enriched 3-[5- 2-(2,3-dihydroxyprop-l-yl)-o-carboran-l-yl pentan-l-yl] thymidine (N5-20H), a new boron delivery agent for boron neutron capture therapy of brain tumors. 

Wu, G. Barth, R. R Yang, W. Lee, R. J. Tjarks, W. Backer, M. V. Backer, J. M. In Neutron capture therapy of cancer Nanoparticles and high molecular weight boron delivery agents in Narwtechonolgy for cancer therapy. Mansoor M. Amiji (Ed.), CRC Press, 2006, Chapter 6, pp. 77-103. 

High Molecular Weight Boron Delivery Agents... 

Synthesis of a few other boronated dendrimers that potentially could be used as boron delivery agents for BNCT were described recently [178,179]. 

---