Boron Accumulation Research Articles

A periodic development of BPA and BSH based derivatives in boron neutron capture therapy (BNCT).

Boron neutron capture therapy (BNCT) is a particular type of radiotherapy that requires a selective and high concentration of boron accumulation in neoplastic cells. To distinguish the distribution of boron compounds between tumour and normal cells, multiple research groups have been involved and successively innovated a wide variety of boron-based compounds. Despite the development of numerous boron compounds, only boronophenylalanine (BPA) and sodium mercaptoundecahydro-closo-dodecaborate (BSH) have emerged as effective in clinical trials. Here, we highlight the detailed progress in the molecular design of BPA and BSH derivatives from the historical perspective to the latest advances in light of the widely accepted performance required for effective BNCT. In this report, we have provided an overview of a variety of derivatives of BPA and BSH, including amino acids, peptides, polymers, monoclonal antibodies and chelated complexes, and it is observed that such derivatives of BPA and BSH are judicious choices for BNCT. Finally, we have summarised the critical issues for BPA and BSH that must be addressed if BNCT is to become a more widely accepted clinical modality.

The role of benzoic acid, gallic acid and salicylic acid in protecting tomato callus cells from excessive boron stress

Excess boron (EB) is a known threat to plant growth and productivity, however, the role of applications of phenolic acids [PAs; benzoic acid (BA), gallic acid (GA), and salicylic acid (SA)] in mitigating this threat has not been extensively explored. In vitro investigations were performed to realize the mechanism of PAs on the tolerance index (TI), boron (B) accumulation, and non-enzymatic antioxidants in alleviating EB on tomato (Solanum lycopersicum L. cultivar Castle Rock) calli. Tomato calli were subjected to two levels of B (medium B condition (control) and 2 mM boric acid) in the presence or absence of different concentrations of PAs. The results showed that moderate levels of BA (1.0 μM), GA (10 μM), and SA (50 μM) promoted inhibition of the TI, flavonoids, and ascorbate (AsA) of EB-treated calli. The B concentration was increased under EB, and this parameter was significantly decreased by PAs. Malondialdehyde (MDA), bound phenolics, cysteine (Cys), glutathione (GSH), and protein thiols (PTs) were increased under EB but were significantly reduced through the use of PAs. Free phenolics were increased under EB and were significantly decreased by PAs, only BA increased its content in calli. In addition, EB reduced non-protein thiols (NPTs); however, this deficiency was alleviated by PAs, only SA reduced its content. These results provide new visions to the mechanism that helps control EB in tomato plants and thus can be harnessed to develop effective plant growth stimuli.

Ecotoxicological assessment of commercial boron nitride nanotubes toward Xenopus laevis tadpoles and host-associated gut microbiota

Despite the growing interest for boron nitride nanotubes (BNNT) due to their unique properties, data on the evaluation of the environmental risk potential of this emerging engineered nanomaterial are currently lacking. Therefore, the ecotoxicity of a commercial form of BNNT (containing tubes, hexagonal-boron nitride, and boron) was assessed in vivo toward larvae of the amphibian Xenopus laevis. Following the exposure, multiple endpoints were measured in the tadpoles as well as in bacterial communities associated to the host gut. Exposure to BNNT led to boron accumulation in host tissues and was not associated to genotoxic effects. However, the growth of the tadpoles increased due to BNNT exposure. This parameter was associated to remodeling of gut microbiome, benefiting to taxa from the phylum Bacteroidetes. Changes in relative abundance of this phylum were positively correlated to larval growth. The obtained results support the finding that BNNT are biocompatible as indicated by the absence of toxic effect from the tested nanomaterials. In addition, byproducts, especially free boron present in the tested product, were overall beneficial for the metabolism of the tadpoles.

Interactive effects of boron stress and mycorrhizal (AMF) treatments on tomato growth, yield, leaf chlorophyll and boron accumulation, and fruit characteristics

ABSTRACT High levels of boron (B) in soils cause toxicity in tomatoes, but inoculation of arbuscular mycorrhizal fungi (AMF) into plants can reduce it. This study aimed to evaluate the effects of AMF inoculation on morphological parameters (shoot height, plant fresh and dry weights), yield, leaf chlorophyll and boron content, and fruit characteristics (weight, water and soluble solid contents, firmness, color) of tomato plants grown in boron stress (0.06, 0.5, 1.0, 2.0, 4.0, and 8.0 mM). Increased boron concentrations reduced all parameters except leaf boron content, fruit soluble solids and firmness. However, the highest values of the morphological parameters, fruit soluble solid contents and red color values (control, 0.5 and 1.0 mM B), fruit yield (<8.0 mM B), leaf chlorophyll content (≤2.0 mM B), fruit weight (control, 0.5 and 2.0 mM B), fruit firmness (control and 1.0 mM B) were obtained from mycorrhizal plants. No significant differences were found between the fruit water content and color values (brightness and yellow) of non-mycorrhizal and mycorrhizal plants in all boron stress levels. The leaf boron concentration in inoculated with mycorrhizal fungi had lower than non-inoculated ones. These results suggest that mycorrhizal-inoculation may limit excessive boron uptake and alternatively be used in boron contaminated soils.

In Vitro and In Vivo Evaluation of Fluorescently Labeled Borocaptate-Containing Liposomes.

Boron neutron capture therapy (BNCT), a binary cancer therapeutic modality, has moved to a new phase since development of accelerator-based neutron sources and establishment of BNCT centers in Finland and Japan. That stimulated efforts for better boron delivery agent development. As liposomes have shown effective boron delivery properties and sufficient tumor retention, fluorescent liposome labelling may serve as a rapid method to study initial ability of newly synthesized liposomes to be captured by tumor cells prior to experiments on boron accumulation and neutron irradiation. In this work, we studied the accumulation and biodistribution of pegylated liposomes with encapsulated borocaptate (BSH) and a fluorescent label (Nile Red) in U87 (human glioblastoma), SW-620 (human colon carcinoma), SK-MEL-28 (human melanoma), FetMSC (mesenchymal human embryo stem cells), and EMBR (primary embryocytes) cell lines as well as an orthotopic xenograft model of U87 glioma in SCID mice. Results indicate that fluorescent microscopy is effective at determining the intracellular localization of the liposomes using a fluorescent label. The synthesized, pegylated liposomes showed higher accumulation in tumors compared to normal cells, with characteristic concentration peaks in SW-620 and U87 cell lines, and provided in vivo tumor selectivity with several-fold higher tumor tissue fluorescence at the 6-h timepoint. Graphical abstract Fluorescent images of U-87 glioma cells after 24 hours of incubation with BSH-containing liposomes labeled with lipophilic Nile Red (red color)and water-soluble FITC-Dextran (green color); cell nuclei in blue color (DAPI-staining) (×400). Scale bar is 50 μm. Fluorescent labelling serves as anexpress method to study liposome delivery efficiency prior to boron accumulation evaluation and BNCT irradiation experiments.

The impact of using low-saline oilfield produced water for irrigation on water and soil quality in California

The consecutive occurrence of drought and reduction in natural water availability over the past several decades requires searching for alternative water sources for the agriculture sector in California. One alternative source to supplement natural waters is oilfield produced water (OPW) generated from oilfields adjacent to agricultural areas. For over 25 years, OPW has been blended with surface water and used for irrigation in the Cawelo Water District of Kern County, as permitted by California Water Board policy. This study aims to evaluate the potential environmental impact, soil quality, and crop health risks of this policy. We examined a large spectrum of salts, metals, radionuclides (226Ra and 228Ra), and dissolved organic carbon (DOC) in OPW, blended OPW used for irrigation, groundwater, and soils irrigated by the three different water sources. We found that all studied water quality parameters in the blended OPW were below current California irrigation quality guidelines. Yet, soils irrigated by blended OPW showed higher salts and boron relative to soils irrigated by groundwater, implying long-term salts and boron accumulation. We did not, however, find systematic differences in 226Ra and 228Ra activities and DOC in soils irrigated by blended or unblended OPW relative to groundwater-irrigated soils. Based on a comparison of measured parameters, we conclude that the blended low-saline OPW used in the Cawelo Water District of California is of comparable quality to the local groundwater in the region. Nonetheless, the salt and boron soil accumulation can pose long-term risks to soil sodification, groundwater salinization, and plant health; as such, the use of low-saline OPW for irrigation use in California will require continual blending with fresh water and planting of boron-tolerant crops to avoid boron toxicity.

YC-1 sensitizes the antitumor effects of boron neutron capture therapy in hypoxic tumor cells.

The uptake of boron into tumor cells is a key factor in the biological effects of boron neutron capture therapy (BNCT). The uptake of boron agents is suppressed in hypoxic conditions, but the mechanism of hypoxia-induced modulation of suppression of boron uptake is not clear. Therefore, we evaluated whether hypoxia-inducible factor 1α (HIF-1α) contributes to attenuation of the antitumor effects of BNCT in hypoxic tumor cells. We also tested whether YC-1, a HIF-1α-targeting inhibitor, has therapeutic potential with BNCT. To elucidate the mechanism of attenuation of the effects of BNCT caused by hypoxia, deferoxamine (DFO) was used in experiments. Cells were incubated in normal oxygen, hypoxic conditions (1% O2) or 5 μM DFO for 24 h. Then, cells were treated with 10B-boronophenylalanine (BPA) for 2 h and boron accumulation in cells was evaluated. To clarify the relationship between HIF-1α and L-type amino acid transporter 1 (LAT1), gene expression was evaluated by a using HIF-1α gene knockdown technique. Finally, to improve attenuation of the effects of BNCT in hypoxic cells, BNCT was combined with YC-1. Boron uptake was continuously suppressed up to 2 h after administration of BPA by 5 μM DFO treatment. In cells treated with 5 μM DFO, LAT1 expression was restored in HIF-1α-knocked down samples in all cell lines, revealing that HIF-1α suppresses LAT1 expression in hypoxic cells. From the results of the surviving fraction after BNCT combined with YC-1, treatment with YC-1 sensitized the antitumor effects of BNCT in cells cultured in hypoxia.

Lack and accumulation of boron in the leaves after foliar spraying in cabbage and cauliflower plants

Boron deficiency causes biological damage in brassicas according to the growth phase. In this condition, foliar spraying of B causes immediate effects of nutrient accumulation on leaves that may vary in brassicas but are not known. Therefore, the nutritional deficiency as well as the accumulation of B in the leaves over 30 days after their spraying on cabbage and cauliflower plants were evaluated. Were, two experiments were carried out to evaluate the lack of B in the nutritive solution on the nutrition, growth and production of the two brassicas. The other experiments evaluated the dry mass and B leaf content at 0.12 (3 h); 0.25 (6 h); 0.5 (12 h) 1, 5, 15 and 30 days after leaf spraying of the micronutrient and also in the plants that did not receive B in the two brassicas. The effect of the lack of boron was evident in the final growth stage of the plants, causing a decrease in productivity, cab­bage was more sensitive to nutrient deficiency than cauliflower, however. Boron is slowly accumulated by the leaves of the ‘Astrus’ cabbage, absorbing 50% of the applied B, about 15 days after its application and ‘Verona’ cauliflower, at three days and 12 hours after its application.

Boron Accumulation in Brain Tumor Cells through Boc-Protected Tryptophan as a Carrier for Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT) is a binary therapeutic approach. Nonradioactive boron-10 atoms accumulated in tumor cells combining with the neutron beams produce two highly energetic particles that could eradicate the cell that takes it and the neighboring cells. Small molecules that carry boron atom, e.g. 5- and 6-boronated and 2,7-diboronated tryptophans, were assessed for their boron accumulation in U87-MG, LN229, and 3T3 for BNCT. TriBoc tryptophan, TB-6-BT, shows boron-10 at 300 ppm in both types of tumor cells with a tumor to normal ratio (T/N) of 5.19-5.25 (4 h). TB-5-BT and DBA-5-BT show boron-10 at 300 ppm (2 h) in U87-MG cells. TB-5-BT exerts a T/N of >9.66 (1 h) in LN229 compared with the current clinical boronophenyl alanine with a highest T/N of 2.3 (1 h) and accumulation concentration of <50 ppm. TB-5-BT and TB-6-BT warrant further animal study.

Foliar Fertilization with Boron on the Growth, Physiology, and Yield of Snap Beans

The snap bean is a vegetable of great worldwide economic importance. However, tropical soils have low amounts of nutrients, especially boron, a micronutrient essential for plant nutrition. The objective of this work is to verify the effects of foliar application of boron on the growth, physiology, nutrition, and productivity of snap beans. The experiment was carried out in a greenhouse in a completely randomized design, with five treatments comprising boron doses (0 – control, 1350, 2700, 4050, and 5400 ppm) and four replicates. Foliar application of boron was carried out at the V3 vegetative stage (third mature trifoliate). Growth, physiological, nutritional, and productivity variables were evaluated at the reproductive stages R5 (flowering) and R8 (harvest). Data were subjected to analysis of variance and F test at a 5% significance level. When significant, data was submitted to Student t, Scott-Knott, and regression analysis. Doses above than 2700 ppm affected significantly foliar temperature, transpiration, stomatal conductance, photosynthesis, and internal carbon concentration of bean pods. Foliar fertilization with boron influenced significantly the content and accumulation of boron in the shoot (868%) and the root system (105%), but it did not change the contents in pods. However, although they affect the physiology of snap bean plants, the tested doses did not influence significantly the growth variables and productivity. Boron doses from 2700 ppm caused symptoms of phytotoxicity on snap bean crops. Therefore, we do not recommend foliar application of boron at the stage V3 in snap bean crops even with a low boron content in the soil.

On-Demand Biodegradable Boron Nitride Nanoparticles for Treating Triple Negative Breast Cancer with Boron Neutron Capture Therapy.

Compared with photon-induced binary cancer therapy, such as photothermal therapy (PTT) and photodynamic therapy (PDT), boron neutron capture therapy (BNCT) emerges as an alternative noninvasive treatment strategy that could overcome the shallow penetration of light. One key factor in performing successful BNCT is to accumulate a sufficient amount of B-10 (>20 ppm) within tumor cells, which has been a long-standing challenge for small-molecule-based boron drugs. Boron nitride nanoparticles (BNNPs) are promising boron carriers due to their high boron content and good biocompatibility, as certain types of BNNPs can undergo rapid degradation under physiological conditions. To design an on-demand degradable boron carrier, BNNPs were coated by a phase-transitioned lysozyme (PTL) that protects BNNPs from hydrolysis during blood circulation and can be readily removed by vitamin C after neutron capture therapy. According to PET imaging, the coated BNNPs exhibited high tumor boron accumulation while maintaining a good tumor to nontumor ratio. Tail-vein injections of vitamin C were followed by neutron irradiation, and BNNPs were found to be rapidly cleared from major organs according to ex vivo ICP-OES analysis. Compared with the control group, animals treated with BNCT showed suppression of tumor growth, while almost negligible side effect was observed. This strategy not only utilized the high boron content of BNNPs but also successfully performed an on-demand degradation of BNNPs to avoid the potential toxicity caused by the long-term accumulation of nanoparticles.

Biodistribution of calcium fructoborate as a targeting agent for boron neutron capture therapy in an experimental model of MDA-MB-231 breast cancer cells

Abstract Boron neutrons capture therapy (BNCT) involves optional agglomeration of 10B carriers in further neutron irradiation to the tumor tissue. The possibility of a Calcium Fructoborate (CFB) mediated by liposome has been proposed previously as boron carriers for the transfer of boron compound to the tumor tissue. Furthermore, for developing the use of a carrier, folate has been considered as an appropriate substrate with the potential to attach to tumor receptors on the surface of certain cancer cells compared with normal cells. The main problem associated with breast cancer is that the tumor and normal cells are mixed without a map of the boron accumulation. The present study aimed to examine boron biodistribution in the breast cancer model in BALB/c mice employing PEGylated liposome-encapsulated CFB formulations that were previously obtained. The predetermined boron concentration was obtained to be 20 mg 10B/g to 35 mg 10B/g. Also, the samples of the tumor tissue, such as the liver, muscle, heart, lung, spleen, skin, stomach, brain, bone, and kidney were taken as post-administration at different times to measure the boron content by inductively coupled plasma (ICP) analysis. The results demonstrated the existence of GLUT-5 expression as an erythrocyte-type glucose transporter protein in a wide range of tumor cells. In summary, the results of the present study suggest the therapeutic potential of boron-bearing liposomes given large boron biodistribution values.

Remarkable Boron Delivery Of iRGD-Modified Polymeric Nanoparticles For Boron Neutron Capture Therapy.

PurposeBoron neutron capture therapy (BNCT) is an emerging binary radiotherapy, which is limited for application due to the challenge of targeted delivery into tumor nowadays. Here, we propose the use of iRGD-modified polymeric nanoparticles for active targeted delivery of boron and doxorubicin (DOX) in BNCT.Methods10B-enriched BSH was covalently grafted to PEG-PCCL to prepare 10B-polymer, then surface-modified with iRGD. And, DOX was physically incorporated into polymers afterwards. Characterization of prepared polymers and in vitro release profile of DOX from polymers were determined by several methods. Cellular uptake of DOX was observed by confocal microscope. Accumulation of boron in cells and tissues was analyzed by ICP-MS. Biodistribution of DOX was studied by ex vivo fluorescence imaging and quantitative measurement. Tumor vascular normalization of Endostar for promoting delivery efficiency of boron on refractory B16F10 tumor was also studied.ResultsThe polymers were monodisperse and spheroidal in water with an average diameter of 24.97 nm, which were relatively stable at physiological pH and showed a sustained release of DOX, especially at endolysosomal pH. Enhanced cellular delivery of DOX was found in iRGD-modified polymer group. Cellular boron uptake of iRGD-modified polymers in A549 cells was remarkably raised fivefold (209.83 ng 10B/106 cells) compared with BSH. The polymers represented prolonged blood circulation, enhanced tumor accumulation of 10B against BSH, and favorable tumor:normal tissue boron concentration ratios (tumor:blood = 14.11, tumor:muscle = 19.49) in A549 tumor-bearing mice 24 hrs after injection. Both fluorescence imaging and quantitative measurement showed the highest tumor accumulation of DOX at 24 hrs after injecting of iRGD-modified polymers. Improvement of vascular integrity and reduction of vascular mimicries were found after Endostar injection, and raised tumor accumulation of boron as well.ConclusionThe developed nanoparticle is an inspiring candidate for the safe clinical application for BNCT.

Boron-Nanoparticle-Loaded Folic-Acid-Functionalized Liposomes to Achieve Optimum Boron Concentration for Boron Neutron Capture Therapy of Cancer.

In this study, we have synthesized and characterized a pure boron nanoparticle containing asolectin phospholipid-based liposome construct prepared using a water-in-oil emulsion method, as a novel alternative agent for BNCT, which contain poly(maleic anhydride-alt-1-octadecene) (PMAO) and polyethylene glycol (PEG) on the surface, and Cy5 near infrared (NIR) fluorescent dye and boron nanoparticles in the core (3PCB). A tumor-specific targeting ligand, folic acid (FA), was conjugated to PEG to produce a folate-functionalized liposome (FA-3PCB) for improved targeted delivery and accumulation of boron in cancer cells. The liposomes showed an average diameter of 100-120 nm and zeta potential of -38.0±1.5 mV. Cellular uptake monitored by fluorescence microscopy confirmed the targeting capability of FA-conjugated liposomes. Accumulation of FA-conjugated liposomes in C6-brain tumor cells was much higher than that of non-FA conjugated liposomes under the same conditions. ICP-MS (Inductively Coupled Plasma Mass Spectrometry) quantification confirmed that boron accumulated in cancer cells to sufficient intracellular concentration for therapeutic benefit from BNCT. These liposomes show blood-brain barrier (BBB) crossing ability, low cytotoxicity, and excellent stability under physiological conditions. Thus, these liposomes are a promising new boron carrier for BNCT.

Boron geochemistry of the geothermal waters from two typical hydrothermal systems in Southern Tibet (China): Daggyai and Quzhuomu

The Tibetan plateau is characterized by a widely and intensively distributed geothermal activity and an extreme enrichment of boron in some geothermal waters. Twenty-five hot spring samples were collected from the Daggyai and Quzhuomu geothermal areas in Tibet to determine their boron concentrations and isotope composition. The boron concentrations and δ11B values for the neutral geothermal waters in Daggyai range from 72.5 to 106.9 mg/L and −16.4‰ to −12.3‰ while the Daggyai acid waters have much lower boron concentrations (1.1–1.2 mg/L) and slightly higher δ11B values (−12.9‰). The hot spring samples from the Quzhuomu geothermal area have boron concentrations varying from 21.9 to 44.6 mg/L and δ11B values from −11.3‰ to −7.1‰. The hydrochemical and B isotopic evidence imply that the boron in Daggyai geothermal waters is contributed by both magmatic fluid input and host rock leaching. In contrast, marine carbonates and granites, especially the former, are confirmed as the major boron sources for the Quzhuomu geothermal waters. In addition, there also exist some secondary processes affecting the boron isotope fractionation in geothermal waters, e.g. water-vapor separation and absorption or incorporation of B into hydrothermally altered minerals. Finally, based on the analysis of B geochemistry in these two typical geothermal areas in Southern Tibet with different heat sources and reservoir lithology, the mechanisms for the accumulation of boron in the Daggyai and Quzhuomu geothermal waters are suggested. This study is promising to provide insight into the sources of boron in the geothermal waters in other Tibetan geothermal areas.

Soil Fertilization and Texture on Boron Accumulation and Wood Volume in Corymbia citriodora (Hook) K.D. Hill &amp; L.A.S Johnson

This study aimed to evaluate the effects of soil fertilization and texture on leaf Boron (B) accumulation and its relation with wood volume of Corymbia citriodora Hill &amp; Johnson. The experiment was set in randomized block with four replications, four B fertilization levels (0, 1.1, 2.2 and 4.4 g.plant-1) in two soils types (sandy and clayey). To determine leaf B content, 25 leaves were collected from the median portion of four trees for each treatment. Leaves were dried on oven and B content was determined by the Azomethine-H method using extract obtained by dry digestion. The diameter at breast height and the total height of 25 trees were collected in all treatments and wood volume was calculated. Data were submitted to analysis of variance and the means adjusted to regression equations. The regression coefficients were evaluated by t-test at 1 and 5% probability. It was verified that clay soil produces more wood, compared to sandy soil. There was a gain increase in foliar B as B doses increased in both soil types. Leaf B affected Corymbia citriodora productivity only in clay soil.

Excess boron inhibited the trifoliate orange growth by inducing oxidative stress, alterations in cell wall structure, and accumulation of free boron

The boron (B) is an essential nutrient and plays an important role in the stability of the primary cell wall (CW). Due to the narrow window between B deficiency and toxicity, mismanagement practices lead to B toxicity that inhibit root growth and overall crop productivity. However, the exact cause of root growth inhibition remains unclear. The present study examined the potential causes and targets of B toxicity by studying intercellular mechanism. The trifoliate seedlings were cultured under excess B conditions. The results indicated that plant growth was inhibited by excess B, nevertheless, the effects were prominent on roots and leaves. B toxicity exacerbated oxidative stress and root cell death. The analysis of CW functional groups, CW microstructure and B forms lead to the conclusion that alterations in CW, and accumulation of free-B and carbohydrates might cause inhibition of growth and visible symptoms of B toxicity.

Biochemical and molecular analyses of potential markers for evaluating the competition for resources between mature fruit and open flowers in ‘Hass’ avocado trees

ABSTRACTAlternate bearing of ‘Hass’ avocado (Persea americana Mill.) trees is a phenomenon across avocado-growing regions around the world. In New Zealand, the cycle can be more complex as the fruit often remains on the trees for over 12 months, potentially resulting in competition for resources between fruit from the previous year and the flowers. This work looks at the impact of the presence of a 12-month-old heavy crop on the accumulation of boron and carbohydrates to flowers. By sequencing and measuring the expression of the avocado Trehalose Phosphate Synthesis (TPS1) gene, we report on the effects of cropping cycle on the delivery of carbohydrates to the flower. Differences in sugar delivery rate to the flower reflected by differences in TPS1 expression were not reflected in the carbohydrate and boron contents of open flowers, and it is suggested that flowers require a certain amount of sugars to accumulate to enable their development and to reach a stage where they are able to open as a female flower.

Genetic parameters for fruit mineral content in an interspecific pear (Pyrus spp.) population

ABSTRACTThere is a lack of data and information on mineral content in pear fruit and none on the genetic parameters related to these individual elements. The aim of this research was to report mineral composition of pear fruit and to determine the quantitative genetic parameters of mineral content in fruit from interspecific pear populations. There was a high genetic component involved in the accumulation of boron and aluminium in the fruit, with heritabilities of as much as 0.72. Iron had a positive genetic correlation with accumulation of zinc (0.72) and sulphur (0.71), while chromium had a negative correlation with nickel (−0.77), phosphorus (−0.70) and magnesium (−0.4) accumulation. Parents of the same origin (Asian or European) had similar estimated breeding values for total mineral content. Macro element mineral content of fruit was: 4% calcium, 13% phosphorus, 76% potassium, 5% magnesium and 2% sulphur and for micro element mineral content 39% boron, 12% iron, 8% zinc, 4% manganese, 7% copper, 0.4% chromium, 9% nickel and 21% aluminium.

Boron-incorporating hemagglutinating virus of Japan envelope (HVJ-E) nanomaterial in boron neutron capture therapy

ABSTRACT Combining immunotherapeutic and radiotherapeutic technique has recently attracted much attention for advancing cancer treatment. If boron-incorporated hemagglutinating virus of Japan-envelope (HVJ-E) having high membrane fusion ability can be used as a boron delivery agent in boron neutron capture therapy (BNCT), a radical synergistic improvement of boron accumulation efficiency into tumor cells and antitumor immunity may be induced. In this study, we aimed to develop novel boron-containing biocompatible polymers modified onto HVJ-E surfaces. The copolymer consisting of 2-methacryloyloxyethyl phosphorylcholine (MPC) and methacrylamide benzoxaborole (MAAmBO), poly[MPC-co-MAAmBO], was successfully synthesized by using a simple free radical polymerization. The molecular structures and molecular weight of the poly[MPC-co-MAAmBO] copolymer were characterized by nuclear magnetic resonance and matrix-assisted laser desorption ionization time-of-flight mass spectrometry, respectively. The poly[MPC-co-MAAmBO] was coated onto the HVJ-E surface via the chemical bonding between the MAAmBO moiety and the sugar moiety of HVJ-E. DLS, AFM, UV-Vis, and fluorescence measurements clarified that the size of the poly[MPC-co-MAAmBO]-coated HVJ-E, HVJ-E/p[MPC-MAAmBO], to be about 130 ~ 150 nm in diameter, and that the polymer having 9.82 × 106 ~ 7 boron atoms was steadily coated on a single HVJ-E particle. Moreover, cellular uptake of poly[MPC-co-MAAmBO] could be demonstrated without cytotoxicity, and the hemolysis could be successfully suppressed by 20%. These results indicate that the HVJ-E/p[MPC-MAAmBO] may be used as boron nanocarriers in a combination of immunotherapy with BNCT.