Human glioblastoma-derived cell membrane nanovesicles: a novel, cell-specific strategy for boron neutron capture therapy of brain tumors.

Glioblastoma (GBM), one of the deadliest brain tumors, accounts for approximately 50% of all primary malignant CNS tumors, therefore novel, highly effective remedies are urgently needed. Boron neutron capture therapy, which has recently repositioned as a promising strategy to treat high-grade gliomas, requires a conspicuous accumulation of boron atoms in the cancer cells. With the aim of selectively deliver sodium borocaptate (BSH, a 12 B atoms-including molecule already employed in the clinics) to GBM cells, we developed novel cell membrane-derived vesicles (CMVs), overcoming the limits of natural extracellular vesicles as drug carriers, while maintaining their inherent homing abilities that make them preferable to fully synthetic nanocarriers. Purified cell membrane fragments, isolated from patient-derived GBM stem-like cell cultures, were used to prepare nanosized CMVs, which retained some membrane proteins specific of the GBM parent cells and were devoid of potentially detrimental genetic material. In vitro tests evidenced the targeting ability of this novel nanosystem and ruled out any cytotoxicity. The CMVs were successfully loaded with BSH, by following two different procedures, i.e. sonication and electroporation, demonstrating their potential applicability in GBM therapy.

Evaluation of sodium borocaptate (BSH) and boronophenylalanine (BPA) as boron delivery agents for neutron capture therapy (NCT) of cancer: an update and a guide for the future clinical evaluation of new boron delivery agents for NCT.

Boron neutron capture therapy (BNCT) is a cancer treatment modality based on the nuclear capture and fission reactions that occur when boron-10, a stable isotope, is irradiated with neutrons of the appropriate energy to produce boron-11 in an unstable form, which undergoes instantaneous nuclear fission to produce high-energy, tumoricidal alpha particles. The primary purpose of this review is to provide an update on the first drug used clinically, sodium borocaptate (BSH), by the Japanese neurosurgeon Hiroshi Hatanaka to treat patients with brain tumors and the second drug, boronophenylalanine (BPA), which first was used clinically by the Japanese dermatologist Yutaka Mishima to treat patients with cutaneous melanomas. Subsequently, BPA has become the primary drug used as a boron delivery agent to treat patients with several types of cancers, specifically brain tumors and recurrent tumors of the head and neck region. The focus of this review will be on the initial studies that were carried out to define the pharmacokinetics and pharmacodynamics of BSH and BPA and their biodistribution in tumor and normal tissues following administration to patients with high-grade gliomas and their subsequent clinical use to treat patients with high-grade gliomas. First, we will summarize the studies that were carried out in Japan with BSH and subsequently at our own institution, The Ohio State University, and those of several other groups. Second, we will describe studies carried out in Japan with BPA and then in the United States that have led to its use as the primary drug that is being used clinically for BNCT. Third, although there have been intense efforts to develop new and better boron delivery agents for BNCT, none of these have yet been evaluated clinically. The present report will provide a guide to the future clinical evaluation of new boron delivery agents prior to their clinical use for BNCT.

Unveiling the Roles of Alloyed Boron in Hexavalent Chromium Removal Using Borohydride-Synthesized Nanoscale Zerovalent Iron: Electron Donor and Antipassivator.

Nanoscale zerovalent iron synthesized using borohydride (B-NZVI) has been widely applied in environmental remediation in recent decades. However, the contribution of boron in enhancing the inherent reactivity of B-NZVI and its effectiveness in removing hexavalent chromium [Cr(VI)] have not been well recognized and quantified. To the best of our knowledge, herein, a core-shell structure of B-NZVI featuring an Fe-B alloy shell beneath the iron oxide shell is demonstrated for the first time. Alloyed boron can reduce H+, contributing to more than 35.6% of H2 generation during acid digestion of B-NZVIs. In addition, alloyed B provides electrons for Fe3+ reduction during Cr(VI) removal, preventing in situ passivation of the reactive particle surface. Meanwhile, the amorphous oxide shell of B-NZVI exhibits an increased defect density, promoting the release of Fe2+ outside the shell to reduce Cr(VI), forming layer-structured precipitates and intense Fe-O bonds. Consequently, the surface-area-normalized capacity and surface reaction rate of B-NZVI are 6.5 and 6.9 times higher than those of crystalline NZVI, respectively. This study reveals the importance of alloyed B in Cr(VI) removal using B-NZVI and presents a comprehensive approach for investigating electron pathways and mechanisms involved in B-NZVIs for contaminant removal.

Ion Current Rectification Activity Induced by Boron Hydride Nanosheets to Enhance Magnesium Analgesia.

The limited analgesic efficiency of magnesium restricts its application in pain management. Here, we report boron hydride (BH) with ion currents rectification activity that can enhance the analgesic efficiency of magnesium without the risks of drug tolerance or addiction. We synthesize MgB2, comprising hexagonal boron sheets alternating with Mg2+. In pathological environment, Mg2+ is exchanged by H+, forming two-dimensional borophene-analogue BH sheets. BH interacts with the charged cations via cation-pi interaction, leading to dynamic modulation of sodium and potassium ion currents around neurons. Additionally, released Mg2+ competes Ca2+ to inhibit its influx and neuronal excitation. In vitro cultured dorsal root neurons show a remarkable increase in threshold potential from the normal -35.9 mV to -5.9 mV after the addition of MgB2, indicating potent analgesic effect. In three typical pain models, including CFA-induced inflammatory pain, CINP- or CCI-induced neuropathic pain, MgB2 exhibits analgesic efficiency approximately 2.23, 3.20, and 2.0 times higher than clinical MgSO4, respectively, and even about 1.04, 1.66, and 1.95 times higher than morphine, respectively. The development of magnesium based intermetallic compounds holds promise in addressing the non-opioid medical need for pain relief.

Enhanced ac4C detection in RNA via chemical reduction and cDNA synthesis with modified dNTPs.

The functional analysis of epitranscriptomic modifications in RNA is constrained by a lack of methods that accurately capture their locations and levels. We previously demonstrated that the RNA modification N4-acetylcytidine (ac4C) can be mapped at base resolution through sodium borohydride reduction to tetrahydroacetylcytidine (tetrahydro-ac4C), followed by cDNA synthesis to misincorporate adenosine opposite reduced ac4C sites, culminating in C:T mismatches at acetylated cytidines (RedaC:T). However, this process is relatively inefficient, resulting in <20% C:T mismatches at a fully modified ac4C site in 18S rRNA. Considering that ac4C locations in other substrates including mRNA are unlikely to reach full penetrance, this method is not ideal for comprehensive mapping. Here, we introduce "RetraC:T" (reduction to tetrahydro-ac4C and reverse transcription with amino-dATP to induce C:T mismatches) as a method with enhanced ability to detect ac4C in cellular RNA. In brief, RNA is reduced through NaBH4 or the closely related reagent sodium cyanoborohydride (NaCNBH3) followed by cDNA synthesis in the presence of a modified DNA nucleotide, 2-amino-dATP, that preferentially binds to tetrahydro-ac4C. Incorporation of the modified dNTP substantially improved C:T mismatch rates, reaching stoichiometric detection of ac4C in 18S rRNA. Importantly, 2-amino-dATP did not result in truncated cDNA products nor increase mismatches at other locations. Thus, modified dNTPs are introduced as a new addition to the toolbox for detecting ac4C at base resolution.

Facile green synthesis of a novel NiO and its catalytic effect on methylene blue photocatalytic reduction and sodium borohydride hydrolysis.

NiO nanoparticles were synthesized from pine cone extract by green synthesis method, which is a simple, cost-effective, environmentally friendly and sustainable method. The particle size of NiO nanoparticles was determined to be in the range of 10-25 nm by X-diffraction differential and transmission electron microscope analysis, and the bandgap energy of NiO nanoparticles was determined to be 2.66 eV. The catalytic effect of NiO nanoparticles in both microwave-assisted sodium borohydride hydrolysis and photocatalytic reduction of methylene blue was examined and it was determined that they had a high catalytic effect in both applications. It was determined that the hydrogen production rate in sodium borohydride hydrolysis was 1135 mL/g/min. The activation energy of sodium borohydride hydrolysis is 29.69 kJ/mol and 29.59 kJ/mol for the nth-order and Langmuir Hinshelwood kinetic models, respectively. In the photocatalytic reduction of methylene blue with NaBH4, it was determined that the reduction did not occur in the absence of a catalyst, but in the presence of the catalyst, the reduction occurred 98% in 3 min. It was determined that NiO nanoparticles were used five times in the photocatalytic reduction of methylene blue and the reduction efficiency for the fifth time was 93%. It was determined that the photocatalytic reduction of methylene blue was pseudo-first order and the rate constant was 1.63 s-1. It was determined that NiO nanoparticles synthesized by the environmentally friendly green synthesis method can be used as catalysts for two different applications.

NiO nanoparticles were synthesized from pinecone extract in a simple, cost-effective, and green method. The synthesized NiO nanoparticles were characterized using various characterization techniques. NiO nanoparticles have high activity both in the photocatalytic reduction of methylene blue and in the hydrolysis of sodium borohydride, and they are catalysts with high activity in two different applications. Photocatalytic reduction of methylene blue with uncatalyzed NaBH₄ was not achieved and was completed in 3 min in the presence of NiO nanoparticle catalyst. It was determined that the hydrogen production rate in sodium borohydride hydrolysis was 1135 mL/g^/min. NiO nanoparticle catalysts have low activation energy for sodium borohydride hydrolysis.

Derivados de prostaglandinas partiendo de la prostaglandina A2: I. Estudio de la reacción de reducción del 15-acetato PGA2 metil ester / Prostaglandin derivatives from prostaglandin A2: I. Study of the reaction of the 15 acetate PGA2 methyl ester

Se efectúa el estudio de la reacción de reducción del 15-acetato PGA2 metil éster con borohidruro de sodio, el cual provoca la pérdida del doble enlace C10-C11 al seguir un mecanismo de adición 1,4 de acuerdo con nuestras condiciones de trabajo y se demuestra que es un reactivo no estereoespecífico. Esto se comprueba mediante el análisis espectroscópico IR y UV, así como por cromatografía de capa delgada de los productos obtenidos y verificados por el posterior producto de oxidación