Novel Carboranes with a DNA Binding Unit for the Treatment of Cancer by Boron Neutron Capture Therapy

Tietze, Lutz F.; Griesbach, Ulrich; Bothe, Ulrich; Nakamura, Hiroyuki; Yamamoto, Yoshinori

doi:10.1002/1439-7633(20020301)3:2/3<219::aid-cbic219>3.0.co;2-#

Cited by 47 publications

(28 citation statements)

References 36 publications

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“…Therefore, given an equal molar accumulation of BSH and BPA within a tumor, BSH will have delivered a 12-fold higher concentration of boron atoms compared to BPA, thereby facilitating the 20-35 ppm 10 B levels required for effective BNCT. However, their administration is limited because of poor water solubility and cytotoxicity [50].…”

Section: Sodium Borocaptatesupporting

confidence: 79%

“…Carboranes linked to a DNA binding unit have also been explored as a novel boron delivery vehicle [50]. DNA targeting is achieved by the interaction of a 5,6,7-trimethoxyindole moiety with DNA, analogous to its function in the anticancer agent duocarmycin A [50].…”

Section: Nucleoside and Carbohydrate Analogsmentioning

confidence: 99%

“…DNA targeting is achieved by the interaction of a 5,6,7-trimethoxyindole moiety with DNA, analogous to its function in the anticancer agent duocarmycin A [50]. Several hydroxymethylcarborane compounds were synthesized, and the two most promising derivatives had cytotoxicity values (ED 50 ) of 32 and 42.5 μM in human bronchial carcinoma cells (A549) and 7.5 and 10 μM in B-16 human melanoma cells.…”

Section: Nucleoside and Carbohydrate Analogsmentioning

confidence: 99%

“…Treatment of B-16 cells with 10 μM of either hydroxymethylcarborane compound resulted in maximal intracellular boron levels of 2.3 and 3.7 ppm per 10 7 cells after just 3 hours. In contrast, a 1000 μM BPA solution required a 24 h incubation to achieve comparable levels (3.1 ppm per 10 7 cells) [50]. Numerous other classes of boronated DNAbinding molecules have been explored [3].Ô verall, 3-carboranyl thymidine analogs and carboraneappended carbohydrate derivatives have the potential advantage of intra-nuclear accumulation (DNA incorporation) that may lower dosing requirements for effective BNCT.…”

Section: Nucleoside and Carbohydrate Analogsmentioning

confidence: 99%

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Advancements in Tumor Targeting Strategies for Boron Neutron Capture Therapy

2015

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Boron neutron capture therapy (BNCT) is a promising cancer therapy modality that utilizes the nuclear capture reaction of epithermal neutrons by boron-10 resulting in a localized nuclear fission reaction and subsequent cell death. Since cellular destruction is limited to approximately the diameter of a single cell, primarily only cells in the neutron field with significant boron accumulation will be damaged. However, the emergence of BNCT as a prominent therapy has in large part been hindered by a paucity of tumor selective boron containing agents. While L-boronophenylalanine and sodium borocaptate are the most commonly investigated clinical agents, new agents are desperately needed due to their suboptimal tumor selectivity. This review will highlight the various strategies to improve tumor boron delivery including: nucleoside and carbohydrate analogs, unnatural amino acids, porphyrins, antibody-dendrimer conjugates, cationic polymers, cell-membrane penetrating peptides, liposomes and nanoparticles.

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Section: Sodium Borocaptatesupporting

confidence: 79%

Section: Nucleoside and Carbohydrate Analogsmentioning

confidence: 99%

Section: Nucleoside and Carbohydrate Analogsmentioning

confidence: 99%

Section: Nucleoside and Carbohydrate Analogsmentioning

confidence: 99%

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Advancements in Tumor Targeting Strategies for Boron Neutron Capture Therapy

2015

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“…Such receptors are also available in the tumor cells. Extensive research effort has been devoted to the creation of complexes between such biomolecules and 10 B atoms [2,5,27]. An example is offered by molecules comprising an antibody to which boron atoms are bound.…”

Section: Classification Of Boron Neutron Capture Therapy Agentsmentioning

confidence: 99%

Compounds for neutron capture therapy and their distribution in tumors and surrounding tissues of animals (A review)

Koryakin

2006

Pharm Chem J

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Boron-containing compounds for neutron capture therapy (NCT) can be divided into three groups: compounds without specific accumulation in tumor, tumor-selective compounds, and compounds capable of incorporating into the structure of tumor cells. For the NCT of cancer patients, sodium mercaptododecaborate (BSH) and p-boronophenylalanine (BPA) were selected from several hundred of boron-containing compounds. In this paper, data on the distribution of BSH and BPA in the organism of animals with model tumors modeling those encountered in oncological patients are reviewed. Methods for increasing the boron uptake in tumor, based on the combined use of boron compounds and modification factors such as hyperthermia, effect of electric pulses on the tumor zone, administration of compounds possessing vasodilating properties and influencing the blood-brain barrier permeability, are considered.Despite progress in the surgery, beam therapy, and chemotherapy, problems encountered in the treatment of malignant neoplasms such as cerebral glioblastoma multiforme, gliomas, melanomas, and their metastatic manifestations are still far from being solved, since all methods are usually equally damaging both tumor and intact cells in the zone of action. One direction in solving the task of selectively treating malignant neoplasms is related to the development of neutron capture therapy (NCT) [1,2]. The NCT method is based on the interaction of two factors: low-energy ( £ 0.025 eV) "thermal" neutrons and a tumoraffin (oncotropic) preparation delivering to the tumor a chemical element with large cross section for thermal neutron capture. A number of such elements exist in the nature, but only two have found use in the NCT due to their physicochemical properties: boron-10 ( 10 B, 3838 barn) and gadolinium-157 ( 157 Gd, 255 000 barn). The interaction of thermal neutrons with Gd atoms leads to the generation of internal-conversion electrons, instantaneous gamma radiation, and Auger electrons with a total energy of 7.94 MeV per decay event [3,4], all these particles possessing a rather large range in tumor tissues. Despite much lower neutron capture cross section, 10 B atoms offer a significant advantage in comparison to 157 Gd, since the products of the former neutron capture reaction -a particles and 7 Li recoil nuclei (Fig. 1) -have a short range comparable with the cell size, which ensures a local evolution of the reaction energy. For this reason, the use of boron-containing compounds capable of selectively accumulating in a tumor provides cell death after the 10 B(n, a, g) 7 Li reaction predominantly in the tumor cells. This circumstance together with low general toxicity of boron mostly account for the fact that the effort in NCT development since the very beginning was mostly devoted to the search for boron-containing compounds capable of delivering born in necessary amount to the tumor cells.Any candidate boron-containing compound for boron neutron capture therapy (BNCT) has to obey two main requirements:(i) Ability to accumulate predo...

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