Biological Evaluation of Dodecaborate-Containing <scp>l</scp>-Amino Acids for Boron Neutron Capture Therapy

Hattori, Yoshihide; Kusaka, Shintaro; Mukumoto, Mari; Uehara, Kouki; Asano, Tanemasa; Suzuki, Minoru; Masunaga, Shin‐ichiro; Ono, Koji; Tanimori, Shinji; Kirihata, Mitsunori

doi:10.1021/jm300749q

Cited by 58 publications

(47 citation statements)

References 15 publications

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“…According to the cellular boron uptake experiments with respect to the incubation time as shown in Figure , the cells treated with the BSH‐LDH nanohybrid exhibited an enormous intracellular amount of boron (42.4 µg 10 B 10 −6 cells), which reached to a plateau after 1 h incubation, while the cellular boron level in intact BSH‐treated cells was too low to be determined by inductively coupled plasma‐atomic emission spectrometry (ICP‐AES). It is notable that the quantity of boron atoms incorporated into cells by BSH‐LDH exceeded not only the prerequisite for the requirement of BNCT (≈0.02 µg 10 B 10 −6 cells), but also the previous results (0.2–1.5 µg 10 B 10 −6 cells) by those applied with other targeting strategies: liposome, porphyrin, organic modification, and etc . In addition, the high boron concentration in cells treated with the BSH‐LDH nanohybrid was maintained over 8 h in a sustained manner.…”

Section: Resultsmentioning

confidence: 68%

“…Approximately, 10 9 10 B atoms per unit cell (representing ≈0.02 µg 10 B atoms per 10 6 cells) are prerequisite for the successful BNCT . And therefore, the following condition is required for BNCT treatment; (i) at least 20 µg of 10 B is needed per g tumor tissues, (ii) the tumor‐to‐normal tissue (T/N) ratio should be above the unity, and the tumor‐to‐blood (T/B) one should be preferably 3:1 or higher, and (iii) the systemic toxicity must be very low …”

Section: Introductionmentioning

confidence: 99%

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Highly Condensed Boron Cage Cluster Anions in 2D Carrier and Its Enhanced Antitumor Efficiency for Boron Neutron Capture Therapy

Choi

Jeon

Piao

2017

Adv Funct Materials

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An attempt is made to apply layered double hydroxide (LDH) as a boron delivery carrier for boron neutron capture therapy (BNCT), which needs a sufficient amount of boron in tumor cells for its successful administration. To meet this requirement, a nanohybrid (BSH-LDH), mercaptoundecahydrocloso-dodecaborate (BSH) anionic molecules in LDH, is developed as a boron delivery system. The cellular boron content upon permeation of BSH-LDH nanoparticles (42.4 µg 10 B 10 −6 cells) in U87 glioblastoma cell line is found to be ≈2000 times larger than the minimum boron requirement (≈0.02 µg 10 B 10 −6 cells) for BNCT and also orders of magnitude higher than the previous results (0.2-1.5 µg 10 B 10 −6 cells) by those applied with other targeting strategies, and eventually results in excellent neutron capture efficiency even under such low dose (30 µg 10 B mL −1 ) and weak irradiation (1 × 10 12 n cm −2 corresponding to 20 min) condition. According to the biodistribution studies in xenograft mice model, the tumor-to-blood ratio of BSH in the BSH-LDH-treated-group is found to be 4.4-fold higher than that in the intact BSH treated one in 2 h after drug treatment. The present BNCT combined with boron delivery system provides a promising integrative therapeutic platform for cancer treatment.

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Section: Resultsmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Highly Condensed Boron Cage Cluster Anions in 2D Carrier and Its Enhanced Antitumor Efficiency for Boron Neutron Capture Therapy

Choi

Jeon

Piao

2017

Adv Funct Materials

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“…Since the path lengths of the particles are approximately 9 to 10 µm, equal to the dimensions of a single cell, 10 B-containing cells are selectively destroyed by BNCT [1].…”

Section: Introductionmentioning

confidence: 99%

“…Tumor cells selectively uptake BPA, which particularly accumulates in their nuclei and is clinically used in BNCT [1].…”

Section: Introductionmentioning

confidence: 99%

Apoptosis through Bcl-2/Bax and Cleaved Caspase Up-Regulation in Melanoma Treated by Boron Neutron Capture Therapy

Faião-Flores

Coelho²,

Arruda‐Neto

et al. 2013

PLoS ONE

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Boron neutron capture therapy (BNCT) is a binary treatment involving selective accumulation of boron carriers in a tumor followed by irradiation with a thermal or epithermal neutron beam. The neutron capture reaction with a boron-10 nucleus yields high linear energy transfer (LET) particles, alpha and 7Li, with a range of 5 to 9 µm. These particles can only travel very short distances and release their damaging energy directly into the cells containing the boron compound. We aimed to evaluate proliferation, apoptosis and extracellular matrix (ECM) modifications of B16F10 melanoma and normal human melanocytes after BNCT. The amounts of soluble collagen and Hsp47, indicating collagen synthesis in the ECM, as well as the cellular markers of apoptosis, were investigated. BNCT decreased proliferation, altered the ECM by decreasing collagen synthesis and induced apoptosis by regulating Bcl-2/Bax in melanoma. Additionally, BNCT also increased the levels of TNF receptor and the cleaved caspases 3, 7, 8 and 9 in melanoma. These results suggest that multiple pathways related to cell death and cell cycle arrest are involved in the treatment of melanoma by BNCT.

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“…The boron content in BPA is low and the thiol group in BSH can form a disul ide linkage, which damages DNA, and both exhibit low tumor-to-brain and tumor-to-blood of current BNCT research. One approach involves the conjugation of a carborane cage of high boron content with biocompatible organic compounds which are regularly used in cellular processes, such as purines, amino acids, carbohydrates, or imidazoles [6][7][8][9][10][11].…”

mentioning

confidence: 99%

Synthesis and Biological Evaluation of Fluorescein-Tagged 1-Methyl-o-carborane for Boron Neutron Capture Therapy

LA¹,

LE²,

SF*³

et al. 2018

Ann Adv Chem

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Fluorescein was conjugated with 1-methyl-o-carborane and the resulting bioconjugate was biologically evaluated through microscopic and fl ow cytometric studies in pancreatic cancer and squamous cell carcinoma cell lines. The uniform distribution of this bioconjugate, as well as its moderate cytotoxicity and higher boron content relative to present boronated delivery agents sodium borocaptate (BSH) and boronophenylalanine (BPA), provide justifi cation for its further evaluation as a potential delivery agent for BNCT.

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Biological Evaluation of Dodecaborate-Containing l-Amino Acids for Boron Neutron Capture Therapy

Cited by 58 publications

References 15 publications

Highly Condensed Boron Cage Cluster Anions in 2D Carrier and Its Enhanced Antitumor Efficiency for Boron Neutron Capture Therapy

Highly Condensed Boron Cage Cluster Anions in 2D Carrier and Its Enhanced Antitumor Efficiency for Boron Neutron Capture Therapy

Apoptosis through Bcl-2/Bax and Cleaved Caspase Up-Regulation in Melanoma Treated by Boron Neutron Capture Therapy

Synthesis and Biological Evaluation of Fluorescein-Tagged 1-Methyl-o-carborane for Boron Neutron Capture Therapy

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