Recent Advances in Boron Delivery Agents for Boron Neutron Capture Therapy (BNCT)

Xuan, Sunting; Vicente, Maria da Graça H.

doi:10.1002/9781119275602.ch3.2

Cited by 18 publications

(18 citation statements)

References 153 publications

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“…60,61,62,63 BNCT is a versatile, non-invasive and promising chemoradiotherapeutic technique that targets and destroys malignant tumor cells, while restricting damage to healthy cells. 64,65,66 To date, there are few examples of boron-rich drugs for BNCT that have been tested, but with unsuccessful results due to the lack of selectivity, damaging healthy tissue. Therefore, nanotechnology opens a new opportunity to find novel potentially effective boron carriers for BNCT.…”

Section: Introductionmentioning

confidence: 99%

Radiolabeled Cobaltabis(dicarbollide) Anion–Graphene Oxide Nanocomposites for In Vivo Bioimaging and Boron Delivery

Ferrer‐Ugalde

Sandoval

Pulagam

et al. 2021

ACS Appl. Nano Mater.

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A new carbon-based hybrid nanocomposite, which consists of monoiodinated boron-cluster derivatives covalently attached to graphene oxide, is hereby introduced. This GO-I-COSAN has been synthesized using a novel boron-rich cobaltabisdicarbollide precursor with one iodide group attached to one of the boron atoms of the cluster (I-COSAN), and designed to be subsequently labeled with radioactive 124 I for its use in Positron Emission Tomography (PET).In-vitro cytotoxicity studies of GO-I-COSAN with HeLa cells at different concentrations up to 48 h proved that the cell mortality was lower than 10 %, indicating minimal cytotoxicity of the nanomaterial. Remarkably, the internalization of the nanomaterial by cells was confirmed by Transmission Electron Microscopy (TEM), which indicated its accumulation in the cytoplasm, without causing changes neither in the size nor in the morphology of cells.Additionally, in vivo tests using C. elegans confirmed that GO-I-COSAN could be ingested by the worms, showing no significant damage and very low toxicity, which supports the results observed in the in-vitro studies. Radioisotopic labeling of I-COSAN using a Pd-catalyzed isotopic exchange reaction with Na[ 124 I]I and its subsequent functionalization onto GO was performed successfully, leading to the formation of a new radioactive nanocomposite GO-[ 124 I]I-COSAN, which was quickly injected in mice. PET images at different times revealed excellent in-vivo stability of the developed nanomaterial. No activity in thyroid and stomach was observed even at long times, proving that iodide did not detach from the material. GO-[ 124 I]I-COSAN presented a favourable biodistribution profile, being mainly accumulated in the liver and slightly in the lung, with long residence time on blood and progressive elimination via gastrointestinal tract. Noteworthy, the high boron content of this material paves the way towards theranostics, since benefits of a traceable boron delivery for boron neutron cancer therapy (BNCT). I-COSAN, 1, was characterized by 1 H, 11 B and 13 C nuclear magnetic resonance (NMR,

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Section: Introductionmentioning

confidence: 99%

Radiolabeled Cobaltabis(dicarbollide) Anion–Graphene Oxide Nanocomposites for In Vivo Bioimaging and Boron Delivery

Ferrer‐Ugalde

Sandoval

Pulagam

et al. 2021

ACS Appl. Nano Mater.

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“…Therefore, they are regarded [15][16][17][18][19][20][21][22][23] as the most promising precursors of the boron-enriched targets for 10 B-neutron capture However, the polyhedral boron and boron-carbon molecular scaffolds, such as closoborates [13], carboranes [14] and their functionalized derivatives, are available, chemically robust and low-toxicity compounds. Therefore, they are regarded [15][16][17][18][19][20][21][22][23] as the most promising precursors of the boron-enriched targets for 10 B-neutron capture therapy (NCT) treatment for a wide range of cancers. The key problem with their practical medicinal application in such types of radiotherapy is a target delivery of the above boron-enriched compounds to the tumor cells of a given cancer, thus allowing a decrease in the amounts that are required for effective 10 B-NCT treatment and preventing additional intoxication of the patient's body.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Structure of the Bis- and Tris-Polyhedral Hybrid Carboranoclathrochelates with Functionalizing Biorelevant Substituents—The Derivatives of Propargylamine Iron(II) Clathrochelates with Terminal Triple C≡C Bond(s)

et al. 2021

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A synthetic strategy for obtaining structurally flexible hybrid iron(II) carboranoclatrochelates functionalized with biorelevant groups, based on a combination of a 1,3-dipolar cycloaddition reaction with nucleophilic substitution of an appropriate chloroclathrochelate precursor, was developed. In its first stage, a stepwise substitution of the dichloroclathrochelate precursor with amine N-nucleophiles of different natures in various solvents was performed. One of its two chlorine atoms with morpholine or diethylamine in dichloromethane gave reactive monohalogenoclathrochelate complexes functionalized with abiorelevant substituents. Further nucleophilic substitution of their remaining chlorine atoms with propargylamine in DMF led to morpholine- and diethylamine-functionalized monopropargylamine cage complexes, the molecules of which contain the single terminal C≡C bond. Their “click” 1,3-cycloaddition reactions in toluene with ortho-carborane-(1)-methylazide catalyzed by copper(II) acetate gave spacer-containing di- and tritopic iron(II) carboranoclatrochelates formed by a covalent linking between their different polyhedral(cage) fragments. The obtained complexes were characterized using elemental analysis, MALDI-TOF mass, UV-Vis, 1H, 1H{11B}, 11B, 11B{1H}, 19F{1H} and 13C{1H}-NMR spectra, and by a single crystal synchrotron X-ray diffraction experiment for the diethylamine-functionalized iron(II) carboranoclathrochelate. Its encapsulated iron(II) ion is situated almost in the center of the FeN6-coordination polyhedron possessing a geometry intermediate between a trigonal prism and a trigonal antiprism with a distortion angle φ of approximately 28º. Conformation of this hybrid molecule is strongly affected by its intramolecular dihydrogen bonding: a flexibility of the carborane-terminated ribbed substituent allowed the formation of numerous C–H…H–B intramolecular interactions. The H(C) atom of this carborane core also forms the intermolecular C–H…F–B interaction with an adjacent carboranoclathrochelate molecule. The N–H…N intermolecular interaction between the diethylamine group of one hybrid molecule and the heterocyclic five-membered 1Н-[1,2,3]-triazolyl fragment of the second molecule of this type caused formation of H-bonded carboranoclathrochelate dimers in the X-rayed crystal.

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“…Since the reaction rate is depend on the product of the concentrations of reactants, and the value of the thermal neutron flux is limited by the capabilities of a nuclear reactor or accelerator, one of the most important requirements for BNCT drugs, in addition to their selectivity of accumulation in a tumor, is to achieve a therapeutic concentration of at least 20–35 μg per gram of tumor. This gives rise to an active interest in the use of polyhedral boron hydrides and their derivatives containing 10 or more boron atoms in one molecule as components of BNCT preparations [ 2 , 3 , 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Bis(Carboranyl)amides 1,1′-μ-(CH2NH(O)C(CH2)n-1,2-C2B10H11)2 (n = 0, 1) and Attempt of Synthesis of Gadolinium Bis(Dicarbollide)

et al. 2021

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Bis(carboranyl)amides 1,1′-μ-(CH2NH(O)C(CH2)n-1,2-C2B10H11)2 (n = 0, 1) were prepared by the reactions of the corresponding carboranyl acyl chlorides with ethylenediamine. Crystal molecular structure of 1,1′-μ-(CH2NH(O)C-1,2-C2B10H11)2 was determined by single crystal X-ray diffraction. Treatment of bis(carboranyl)amides 1,1′-μ-(CH2NH(O)C(CH2)n-1,2-C2B10H11)2 with ammonium or cesium fluoride results in partial deboronation of the ortho-carborane cages to the nido-carborane ones with formation of [7,7′(8′)-μ-(CH2NH(O)C(CH2)n-7,8-C2B9H11)2]2−. The attempted reaction of [7,7′(8′)-μ-(CH2NH(O)CCH2-7,8-C2B9H11)2]2− with GdCl3 in 1,2-dimethoxy- ethane did not give the expected metallacarborane. The stability of different conformations of Gd-containing metallacarboranes has been estimated by quantum-chemical calculations using [3,3-μ-DME-3,3′-Gd(1,2-C2B9H11)2]− as a model. It was found that in the most stable conformation the CH groups of the dicarbollide ligands are in anti,anti-orientation with respect to the DME ligand, while any rotation of the dicarbollide ligand reduces the stability of the system. This makes it possible to rationalize the design of carborane ligands for the synthesis of gadolinium metallacarboranes on their base.

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Recent Advances in Boron Delivery Agents for Boron Neutron Capture Therapy (BNCT)

Cited by 18 publications

References 153 publications

Radiolabeled Cobaltabis(dicarbollide) Anion–Graphene Oxide Nanocomposites for In Vivo Bioimaging and Boron Delivery

Radiolabeled Cobaltabis(dicarbollide) Anion–Graphene Oxide Nanocomposites for In Vivo Bioimaging and Boron Delivery

Synthesis and Structure of the Bis- and Tris-Polyhedral Hybrid Carboranoclathrochelates with Functionalizing Biorelevant Substituents—The Derivatives of Propargylamine Iron(II) Clathrochelates with Terminal Triple C≡C Bond(s)

Synthesis of Bis(Carboranyl)amides 1,1′-μ-(CH2NH(O)C(CH2)n-1,2-C2B10H11)2 (n = 0, 1) and Attempt of Synthesis of Gadolinium Bis(Dicarbollide)

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