Extracellular Vesicles Comprising Carborane Prepared by a Host Exchanging Reaction as a Boron Carrier for Boron Neutron Capture Therapy.

With their low immunogenicity and excellent deliverability, extracellular vesicles (EVs) are promising platforms for drug delivery systems. In this study, hydrophobic molecule loading techniques were developed via an exchange reaction based on supramolecular chemistry without using organic solvents that can induce EV disruption and harmful side effects. To demonstrate the availability of an exchanging reaction to prepare drug-loading EVs, hydrophobic boron cluster carborane (CB) was introduced to EVs (CB@EVs), which is expected as a boron agent for boron neutron capture therapy (BNCT).

Tumour-suppressive effects of curcumin analogs CCA-1.1 and Pentagamavunone-1 in colon cancer: and studies.

This study aimed to evaluate the efficacy of Chemoprevention Curcumin Analog-1.1 (CCA-1.1) and Pentagamavunone-1 (PGV-1) and in colorectal cancer model.

Transcriptomics analyses reveal the effects of Pentagamaboronon-0-ol on PI3K/Akt and cell cycle of HER2+ breast cancer cells.

Introduction: Monoclonal antibodies and targeted therapies against HER2+ breast cancer has improved overall and disease-free survival in patients; however, encountering drug resistance causes recurrence, necessitating the development of newer HER2-targeted medications. A curcumin analog PGB-0-ol showed most cytotoxicity against HCC1954 HER2+ breast cancer cells than against other subtypes of breast cancer cells.

Objective: Here, we employed next-generation sequencing technology to elucidate the molecular mechanism underlying the effect of PGB-0-ol on HCC1954 HER2+ breast cancer cells.

Multi-Targeted Neutron Capture Therapy Combined with an 18 kDa Translocator Protein-Targeted Boron Compound Is an Effective Strategy in a Rat Brain Tumor Model.

Background: Boron neutron capture therapy (BNCT) has been adapted to high-grade gliomas (HG); however, some gliomas are refractory to BNCT using boronophenylalanine (BPA). In this study, the feasibility of BNCT targeting the 18 kDa translocator protein (TSPO) expressed in glioblastoma and surrounding environmental cells was investigated.

Methods: Three rat glioma cell lines, an F98 rat glioma bearing brain tumor model, DPA-BSTPG which is a boron-10 compound targeting TSPO, BPA, and sodium borocaptate (BSH) were used.

The impact of TP53 status of tumor cells including the type and the concentration of administered 10B delivery agents on compound biological effectiveness in boron neutron capture therapy.

Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53) or neo vector (SAS/neo) were inoculated subcutaneously into left hind legs of nude mice. After the subcutaneous administration of a 10B-carrier, boronophenylalanine-10B (BPA) or sodium mercaptododecaborate-10B (BSH), at two separate concentrations, the 10B concentrations in tumors were measured using γ-ray spectrometry. The tumor-bearing mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all intratumor proliferating (P) tumor cells, then were administered with BPA or BSH.

Dodecaborate-Encapsulated Extracellular Vesicles with Modification of Cell-Penetrating Peptides for Enhancing Macropinocytotic Cellular Uptake and Biological Activity in Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT) is a radiation therapy for cancer. In BNCT, the internalization of boron-10 atoms by cancer cells induces cell death through the generation of α particles and recoiling lithium-7 nuclei when irradiated with low-energy thermal neutrons. In this study, we aimed to construct exosomes [extracellular vesicles (EVs)]-based drug delivery technology in BNCT.

Synthesis and cytotoxicity of the boron carrier pentagamaboronon-0-ol for boron neutron capture therapy against breast cancer.

Boronic acid-containing curcumin analog, pentagamaboronon-0 (PGB-0), acts as a potential boron-carrier agent but has limited water solubility. Thus, a new compound (PGB-0-ol) with better chemical and pharmacological properties than PGB-0 has been synthesized. Molecular docking was performed using a molecular operating environment.

Dodecaborate Conjugates Targeting Tumor Cell Overexpressing Translocator Protein for Boron Neutron Capture Therapy.

We developed novel -dodecaborate ([BH]) anion-containing translocator protein (TSPO) ligand as a boron carrier for boron neutron capture therapy. This compound shows high water solubility and can deliver boron to TSPO highly expressed in breast cancer cells. We describe the synthesis and evaluation of a dodecaborate-based pyrazolopyrimidine.

The Evaluation of Cytotoxic Properties from CCB-2 Sugar Complexes Against TNBC and Non-TNBC Cells.

Objective: The progress from Boron Neutron Capture Therapy (BNCT) development urged us to explore new targeted and selective boron carriers. Firstly, we reported the successful synthesis of CCB-2 which exerts a cytotoxic effect against triple negative breast cancer (TNBC) cells. We introduced the new modification of CCB-2 with sugar and alcohol sugars to enhance its solubility in hoping to increase cellular uptake.

The Therapeutic Effects of Dodecaborate Containing Boronophenylalanine for Boron Neutron Capture Therapy in a Rat Brain Tumor Model.

Background: The development of effective boron compounds is a major area of research in the study of boron neutron capture therapy (BNCT). We created a novel boron compound, boronophenylalanine-amide alkyl dodecaborate (BADB), for application in BNCT and focused on elucidating how it affected a rat brain tumor model.

Methods: The boron concentration of F98 rat glioma cells following exposure to boronophenylalanine (BPA) (which is currently being utilized clinically) and BADB was evaluated, and the biodistributions in F98 glioma-bearing rats were assessed.

Antibody-Based Receptor Targeting Using an Fc-Binding Peptide-Dodecaborate Conjugate and Macropinocytosis Induction for Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT) is a radiation method used for cancer therapy. Cellular uptake of boron-10 (B) atoms induces cancer cell death by the generation of alpha particles and recoiling lithium-7 (Li) nuclei when the cells are irradiated with low-energy thermal neutrons. Current BNCT technology shows effective therapeutic benefits in refractory cancers such as brain tumors and head and neck cancers.

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

Boron neutron capture therapy (BNCT) is a form of tumor-cell selective particle irradiation using low-energy neutron irradiation of boron-10 (B) to produce high-linear energy transfer (LET) alpha particles and recoiling Li nuclei (B [n, alpha] Li) in tumor cells. Therefore, it is important to achieve the selective delivery of large amounts of B to tumor cells, with only small amounts of B to normal tissues. To develop practical materials utilizing B carriers, we designed and synthesized novel dodecaboranethiol (BSH)-containing kojic acid (KA-BSH).

Chemical structure of hydrolysates of cereulide and their time course profile.

Hydrolysates of an emetic toxin cereulide were found in the broth of Bacillus cereus. The ester cleaved depsipeptides of cereulide were synthesized using liquid phase fragment condensation method starting from commercially available amino acids. The chemical structure of hydrolysates was verified tetradepsipeptide l-O-Val-l-Val-D-O-Leu-d-Ala and dodecadepsipeptide (D-O-Leu-d-Ala-l-O-Val-l-Val) using LC-TOFMS.

Intracellular target delivery of cell-penetrating peptide-conjugated dodecaborate for boron neutron capture therapy (BNCT).

In this study, we designed and synthesized organelle-targeted cell-penetrating peptide (CPP)-conjugated boron compounds to increase their cellular uptake and to control the intracellular locations for the induction of sophisticated anticancer biological activity in boron neutron capture therapy (BNCT), leading to anticancer effects with ATP reduction and apoptosis when irradiated with neutrons in an in vitro BNCT assay.

Preparation of pentagamaboronon-0 and its fructose and sorbitol complexes as boron carrier for boron neutron capture therapy (BNCT) application.

Development of specific and selective boron carriers is indispensable for boron neutron capture therapy (BNCT) application. Pentagamaboronon-0 (PGB-0) is a promising candidate as boron carrier compound due to the low but selective cytotoxicity in breast cancer cells. Formerly we reported synthesis of PGB-0 which was ineffective due to its low aqueous solubility.

Cellular uptake evaluation of pentagamaboronon-0 (PGB-0) for boron neutron capture therapy (BNCT) against breast cancer cells.

Pentagamaboronon-0 (PGB-0), a curcumin analog compound, has been synthesized as a candidate of boron-carrier pharmaceutical (BCP) for boron neutron capture therapy (BNCT); however, this compound is poorly soluble in water. To improve its solubility, aqueous formulations of PGB-0 with a monosaccharide, fructose or sorbitol, were successfully synthesized, namely PGB-0-F and PGB-0-So, respectively. The cytotoxicity study showed that PGB-0-F and PGB-0-So exerted low cytotoxicity against MCF-7 and MDA-MB 231 breast cancer cells.

Synthesis of the reported structure of homocereulide and its vacuolation assay.

Homocereulide, isolated from marine bacterium Bacillus cereus, is an analog of emetic toxin cereulide. There is no report on its structure determination and involvement in B. cereus-associated food poisoning.

Development and Elucidation of a Novel Fluorescent Boron-Sensor for the Analysis of Boronic Acid-Containing Compounds.

Novel boron-containing drugs have recently been suggested as a new class of pharmaceuticals. However, the majority of current boron-detection techniques require expensive facilities and/or tedious pretreatment methods. Thus, to develop a novel and convenient detection method for boron-based pharmaceuticals, imine-type boron-chelating-ligands were previously synthesized for use in a fluorescent sensor for boronic acid containing compounds.

Practical calculation method to estimate the absolute boron concentration in tissues using F-FBPA PET.

Purpose: The purpose of this study was to establish a practical method to estimate the absolute boron concentrations in the tissues based on the standardized uptake values (SUVs) after administration of 4-borono-phenylalanine (BPA) using 4-borono-2-F-fluoro-phenylalanine (F-FBPA) PET.

Methods: Rat xenograft models of C6 glioma (n = 7, body weight 241 ± 28.0 g) were used for the study.

Boron neutron capture therapy (BNCT) as a new approach for clear cell sarcoma (CCS) treatment: Trial using a lung metastasis model of CCS.

Clear cell sarcoma (CCS) is a rare malignant tumor with a poor prognosis. In the present study, we established a lung metastasis animal model of CCS and investigated the therapeutic effect of boron neutron capture therapy (BNCT) using p-borono-L-phenylalanine (L-BPA). Biodistribution data revealed tumor-selective accumulation of (10)B.

The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model.

Purpose: Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed.

Detection of boronic acid derivatives in cells using a fluorescent sensor.

The detection of boron-containing compounds requires very expensive facilities and/or tedious sample pretreatments. In an effort to develop a convenient detection method for boronic acid derivatives, boron chelating-ligands were synthesized for use as fluorescent sensors. In this paper, the synthesis and properties of fluorescent sensors for boronic acid derivatives are reported.

Synthesis and in vitro evaluation of thiododecaborated α, α- cycloalkylamino acids for the treatment of malignant brain tumors by boron neutron capture therapy.

Boron-neutron capture therapy (BNCT) is an attractive technique for cancer treatment. As such, α, α-cycloalkyl amino acids containing thiododecaborate ([B12H11](2-)-S-) units were designed and synthesized as novel boron delivery agents for BNCT. In the present study, new thiododecaborate α, α-cycloalkyl amino acids were synthesized, and biological evaluation of the boron compounds as boron carrier for BNCT was carried out.