Recent Advances in the Synthesis of High Boron-Loaded Nucleic Acids for BNCT

Boron clusters attract considerable attention as promising therapeutic tools for boron neutron capture therapy (BNCT). They combine high boron content with high chemical and biological stability, biorthogonality, and low toxicity. The development of oligonucleotide-based constructs and nucleic acid-like molecules, such as oligomeric phosphate diesters, bearing one or multiple boron clusters permits to create potential high boron-loaded agents for BNCT with good bioavailability, specifically interacting with nucleic acids inside the cell. Here, we shortly review the strategies and solutions in the design of oligonucleotide conjugates with boron clusters in light of the requirements for effective BNCT and future prospects of their practical use.

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Closomers of High Boron Content: Synthesis, Characterization, and Potential Application as Unimolecular Nanoparticle Delivery Vehicles for Boron Neutron Capture Therapy

Inorganic Chemistry ◽

10.1021/ic051214q ◽

2006 ◽

Vol 45 (1) ◽

pp. 278-285 ◽

Cited By ~ 42

Author(s):

Ling Ma ◽

Julie Hamdi ◽

Francis Wong ◽

M. Frederick Hawthorne

Keyword(s):

Boron Neutron Capture Therapy ◽

Neutron Capture ◽

Potential Application ◽

Boron Content ◽

Neutron Capture Therapy ◽

Nanoparticle Delivery ◽

Boron Neutron Capture ◽

High Boron ◽

Delivery Vehicles

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Biodistribution of 10B in Glioma Orthotopic Xenograft Mouse Model after Injection of L-Para-Boronophenylalanine and Sodium Borocaptate

Biomedicines ◽

10.3390/biomedicines9070722 ◽

2021 ◽

Vol 9 (7) ◽

pp. 722

Author(s):

Natalya V. Gubanova ◽

Alphiya R. Tsygankova ◽

Evgenii L. Zavjalov ◽

Alexander V. Romashchenko ◽

Yuriy L. Orlov

Keyword(s):

Mouse Model ◽

Boron Content ◽

Xenograft Mouse Model ◽

Normal Tissues ◽

Orthotopic Xenograft ◽

Boron Neutron Capture ◽

Epithermal Neutrons ◽

Detailed Statistical Analysis ◽

Low Toxicity ◽

The Brain

Boron neutron capture therapy (BNCT) is based on the ability of the boron-10 (10B) isotope to capture epithermal neutrons, as a result of which the isotope becomes unstable and decays into kinetically active elements that destroy cells where the nuclear reaction has occurred. The boron-carrying compounds—L-para-boronophenylalanine (BPA) and sodium mercaptoundecahydro-closo-dodecaborate (BSH)—have low toxicity and, today, are the only representatives of such compounds approved for clinical trials. For the effectiveness and safety of BNCT, a low boron content in normal tissues and substantially higher content in tumor tissue are required. This study evaluated the boron concentration in intracranial grafts of human glioma U87MG cells and normal tissues of the brain and other organs of mice at 1, 2.5 and 5 h after administration of the boron-carrying compounds. A detailed statistical analysis of the boron biodistribution dynamics was performed to find a ‘window of opportunity’ for BNCT. The data demonstrate variations in boron accumulation in different tissues depending on the compound used, as well as significant inter-animal variation. The protocol of administration of BPA and BSH compounds used did not allow achieving the parameters necessary for the successful course of BNCT in a glioma orthotopic xenograft mouse model.

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Synthesis and toxicity of cobaltabisdicarbollide-containing porphyrins of high boron content

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s1088424611003902 ◽

2011 ◽

Vol 15 (09n10) ◽

pp. 973-983 ◽

Cited By ~ 4

Author(s):

N.V.S. Dinesh K. Bhupathiraju ◽

Vijay Gottumukkala ◽

Erhong Hao ◽

Xiaoke Hu ◽

Frank R. Fronczek ◽

...

Keyword(s):

Boron Content ◽

Maximum Tolerated Dose ◽

Male And Female ◽

High Boron ◽

Low Toxicity ◽

Delivery Vehicles ◽

Animal Toxicity ◽

Low Cytotoxicity ◽

High Yields ◽

Further Development

Two porphyrins of high boron content (OCP and HCP–PEG) were prepared in high yields from the reaction of the corresponding tri- and tetra-(dihydroxyphenyl)porphyrins with zwitterionic cobaltabisdicarbollide [3,3′-Co(8-C4H8O2-1,2-C2B9H10)(1′,2′-C2B9H11)] . Both porphyrins were found to have low cytotoxicity toward human HEp2 cells, and to localize subcellularly mainly in the cell lysosomes. Animal toxicity investigations using male and female BALB/c mice also revealed low toxicity for both compounds. The determined maximum tolerated dose (MTD) for these boronated porphyrins administered intraperitoneally were 160 mg/kg for OCP and 320 mg/kg for HCP–PEG. Our studies warrant further development of these porphyrins of high boron content, and in particular of HCP–PEG, as boron delivery vehicles for BNCT.

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Synthesis of oligo-closo-dodecaborates by Hüisgen click reaction as encapsulated agents for the preparation of high-boron-content liposomes for neutron capture therapy

New Journal of Chemistry ◽

10.1039/c5nj00856e ◽

2015 ◽

Vol 39 (8) ◽

pp. 6388-6394 ◽

Cited By ~ 6

Author(s):

Hayato Koganei ◽

Shoji Tachikawa ◽

Mohamed E. El-Zaria ◽

Hiroyuki Nakamura

Keyword(s):

Neutron Capture ◽

Boron Content ◽

Click Reaction ◽

Neutron Capture Therapy ◽

High Boron

High boron-content molecules and their encapsulated liposomes.

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Blue Emitting Star-Shaped and Octasilsesquioxane-Based Polyanions Bearing Boron Clusters. Photophysical and Thermal Properties

Molecules ◽

10.3390/molecules25051210 ◽

2020 ◽

Vol 25 (5) ◽

pp. 1210 ◽

Cited By ~ 2

Author(s):

Justo Cabrera-González ◽

Mahdi Chaari ◽

Francesc Teixidor ◽

Clara Viñas ◽

Rosario Núñez

Keyword(s):

Ring Opening ◽

Boron Content ◽

Photophysical Properties ◽

Bathochromic Shift ◽

Fluorescence Emission ◽

Boron Clusters ◽

Ring Opening Reaction ◽

Low Emission ◽

High Boron ◽

Thermal Stability Of

High boron content systems were prepared by the peripheral functionalisation of 1,3,5-triphenylbenzene (TPB) and octavinylsilsesquioxane (OVS) with two different anionic boron clusters: closo-dodecaborate (B12) and cobaltabisdicarbollide (COSAN). TPB was successfully decorated with three cluster units by an oxonium ring-opening reaction, while OVS was bonded to eight clusters by catalysed metathesis cross-coupling. The resulting compounds were spectroscopically characterised, and their solution-state photophysical properties analysed. For TPB, the presence of COSAN dramatically quenches the fluorescence emission (λem = 369 nm; ΦF = 0.8%), while B12-substituted TPB shows an appreciable emission efficiency (λem = 394 nm; ΦF = 12.8%). For octasilsesquioxanes, the presence of either COSAN or B12 seems to be responsible for ∼80 nm bathochromic shift with respect to the core emission, but both cases show low emission fluorescence (ΦF = 1.4–1.8%). In addition, a remarkable improvement of the thermal stability of OVS was observed after its functionalisation with these boron clusters.

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Multifunctional Silica Nanoparticles Modified via Silylated-Decaborate Precursors

Journal of Nanomaterials ◽

10.1155/2015/608432 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Fatima Abi-Ghaida ◽

Sébastien Clément ◽

Ali Safa ◽

Daoud Naoufal ◽

Ahmad Mehdi

Keyword(s):

Silica Nanoparticles ◽

Solid State Nmr ◽

Neutron Capture Therapy ◽

Stöber Method ◽

Boron Clusters ◽

New Class ◽

Boron Neutron Capture ◽

The Stöber Method ◽

Luminescent Centers

A new class of multifunctional silica nanoparticles carrying boron clusters (10-vertex closo-decaborate) and incorporating luminescent centers (fluorescein) has been developed as potential probes/carriers for potential application in boron neutron capture therapy (BNCT). These silica nanoparticles were chargedin situwith silylated-fluorescein fluorophoresviathe Stöber method and their surface was further functionalized with decaborate-triethoxysilane precursors. The resulting decaborate dye-doped silica nanoparticles were characterized by TEM, solid state NMR, DLS, nitrogen sorption, elemental analysis, and fluorescence spectroscopy.

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Carbaboranes – more than just phenyl mimetics

Pure and Applied Chemistry ◽

10.1515/pac-2014-1006 ◽

2015 ◽

Vol 87 (2) ◽

pp. 163-171 ◽

Cited By ~ 10

Author(s):

René Frank ◽

Verena Ahrens ◽

Solveig Boehnke ◽

Sven Hofmann ◽

Martin Kellert ◽

...

Keyword(s):

Neutron Capture ◽

Breast Tumour ◽

Water Soluble ◽

Propanoic Acid ◽

Neutron Capture Therapy ◽

Boron Clusters ◽

Boron Neutron Capture ◽

Modified Peptides ◽

Highly Hydrophobic ◽

Selective Accumulation

AbstractDicarba-closo-dodecaboranes(12) (C2B10H12, carbaboranes) are highly hydrophobic and stable icosahedral carbon-containing boron clusters. The cage framework of these clusters can be modified with a variety of substituents, both at the carbon and at the boron atoms. Substituted carbaboranes are of interest in medicine as boron neutron capture therapy (BNCT) agents or as pharmacophores. High and selective accumulation in tumour cells is an important requirement for a BNCT agent and is achieved by incorporating boron-rich, water-soluble carbaborane derivatives into breast tumour-selective modified neuropeptide Y, [F7, P34]-NPY. Preliminary studies showed that the receptor binding affinity and signal transduction of the boron-modified peptides were very well retained. Use of carbaboranes as pharmacophores was shown by replacement of Bpa32 (Bpa=benzoylphenylalanine) in the reduced-size NPY analogue [Pro30, Nle31, Bpa32, Leu34]-NPY 28–36 by ortho-carbaboranyl propanoic acid. The inclusion of the carbaborane derivative resulted in a short NPY agonist with an interesting hY2R/hY4R preference. This might be a promising approach in the field of anti-obesity drug development.

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