Synthesis and Evaluation of Dodecaboranethiol Containing Kojic Acid (KA-BSH) as a Novel Agent for Boron Neutron Capture Therapy

Abstract

Boron neutron capture therapy (BNCT) is a form of tumor-cell selective particle irradiation using low-energy neutron irradiation of boron-10 (10B) to produce high-linear energy transfer (LET) alpha particles and recoiling 7Li nuclei (10B [n, alpha] 7Li) in tumor cells. Therefore, it is important to achieve the selective delivery of large amounts of 10B to tumor cells, with only small amounts of 10B to normal tissues. To develop practical materials utilizing 10B carriers, we designed and synthesized novel dodecaboranethiol (BSH)-containing kojic acid (KA-BSH). In the present study, we evaluated the effects of this novel 10B carrier on cytotoxicity, 10B concentrations in F98 rat glioma cells, and micro-distribution of KA-BSH in vitro. Furthermore, biodistribution studies were performed in a rat brain tumor model. The tumor boron concentrations showed the highest concentrations at 1 h after the termination of administration. Based on these results, neutron irradiation was evaluated at the Kyoto University Research Reactor Institute (KURRI) with KA-BSH. Median survival times (MSTs) of untreated and irradiated control rats were 29.5 and 30.5 days, respectively, while animals that received KA-BSH, followed by neutron irradiation, had an MST of 36.0 days (p = 0.0027, 0.0053). Based on these findings, further studies are warranted in using KA-BSH as a new B compound for malignant glioma.

Translational Evaluation of a Dodecaborated Albumin Conjugate With Maleimide as a Boron Delivery System for a Neutron Capture Reaction to an F98 Rat Glioma Model

“…Suitable requirements for BNCT boron compounds are low intrinsic toxicity, high boron accumulation for target lesions, low uptake into normal tissues, and water solubility [17,30]. In addition, it is also important to consider the method of delivering compounds into the tumor cells because both the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB) prevent the uptake of compounds [31][32][33].…”

“…Moreover, F98 rat glioma models progress histologically to undifferentiated or anaplastic gliomas in in vivo pathological histology [16]. They often serve as brain tumor models for evaluating the BNCT therapeutic effects [17][18][19][20]. F98 rat glioma cells were kindly provided by Dr. Rolf Barth (The Ohio State University, Columbus, Ohio, USA).…”

Desenvolvimento De Desodorante Roll on De Ácido Kójico Como Alternativa Para Clareamento De Axilas

“…Em vista disso, uma alternativa, para o tratamento de manchas é o Ácido Kójico dipalmitado (AK), comumente produzido por meio do metabolismo do Aspergillus orizae e Aspergillus esporulantes (BORGES, 2012;TAKEUCHI, 2020). A ação deste se dá pela inibição da tirosinase por meio da quelação do íon cobre nos sítios ativos da enzima, inibindo a conversão necessária para a formação da melanina (GONCHOROSKI;CORRÊA, 2005;CHANG et al, 2013;PAULA, 2019;OLIVEIRA;VIEIRA, 2020).…”

In Vitro Studies to Define the Cell-Surface and Intracellular Targets of Polyarginine-Conjugated Sodium Borocaptate as a Potential Delivery Agent for Boron Neutron Capture Therapy

“…To expand the possibility of BSH usage in BNCT, numerous studies developing cell-permeable compounds of BSH or carborane were performed. For example, Kirihata and his colleagues recently developed a Kojic acid (KA)-BSH and showed that KA-BSH-BNCT successfully improved survival in a glioma xenograft rat model [ 10 ]. Matsumura and his colleagues developed a α-D-mannopyranoside-conjugated closo-dodecarborate compound and demonstrated longer tumor retention compared to BSH and BPA [ 11 ].…”

“…Boron neutron capture therapy (BNCT) is a cancer therapeutic modality that utilizes a combination of boron 10 B delivery and epithermal neutron irradiation. It results in a spatially and temporally controlled intracellular 10 B nuclear reaction, which generates high-energy alpha particles [1][2][3]. To achieve a safe and efficient therapeutic response, high specificity and selectivity of the 10 B distribution to cancer cells is required.…”