boron and dodecaborate

Topics: Animals; Boron; Boron Compounds; Boron Neutron Capture Therapy; HeLa Cells; Humans; Mice; Serum Albumin

Boron neutron capture therapy (BNCT) is a binary radiotherapeutic approach to the treatment of malignant tumors, especially glioblastoma, the most frequent and incurable brain tumor. For successful BNCT, a boron-containing therapeutic agent should provide selective and effective accumulation of

Topics: Aptamers, Nucleotide; Boron; Boron Compounds; Boron Neutron Capture Therapy; Brain Neoplasms; Cell Line; Cell Line, Tumor; Cell Proliferation; Glioblastoma; Humans; Isotopes; Neutrons

Topics: Animals; Boron; Boron Compounds; Boron Neutron Capture Therapy; Cell Line, Tumor; Drug Carriers; Female; Humans; Integrin alphaVbeta3; Intravital Microscopy; Isotopes; Mice; Neoplasms; Peptides, Cyclic; Serum Albumin, Bovine; Xenograft Model Antitumor Assays

Folic acid (FA) has high affinity for the folate receptor (FR), which is limited expressed in normal human tissues, but over-expressed in several tumor cells, including glioblastoma cells. In the present work, a novel pteroyl-closo-dodecaborate conjugate (PBC) was developed, in which the pteroyl group interacts with FR, and the efficacy of boron neutron capture therapy (BNCT) using PBC was investigated. Thus, in vitro and in vivo studies were performed using F98 rat glioma cells and F98 glioma-bearing rats. For the in vivo study, boronophenylalanine (BPA) was intravenously administered, while PBC was administered by convection-enhanced delivery (CED)-a method for direct local drug infusion into the brain of rats. Furthermore, a combination of PBC administered by CED and BPA administered by intravenous (i.v.) injection was also investigated. In the biodistribution experiment, PBC administration at 6 h after CED termination showed the highest cellular boron concentrations (64.6 ± 29.6 µg B/g). Median survival time (MST) of untreated controls was 23.0 days (range 21-24 days). MST of rats administered PBC (CED) followed by neutron irradiation was 31 days (range 26-36 days), which was similar to that of rats administered i.v. BPA (30 days; range 25-37 days). Moreover, the combination group [PBC (CED) and i.v. BPA] showed the longest MST (38 days; range 28-40 days). It is concluded that a significant MST increase was noted in the survival time of the combination group of PBC (CED) and i.v. BPA compared to that in the single-boron agent groups. These findings suggest that the combination use of PBC (CED) has additional effects.

Topics: Animals; Boron; Boron Compounds; Boron Neutron Capture Therapy; Cell Line, Tumor; Cell Transformation, Neoplastic; Folate Receptors, GPI-Anchored; Glioma; Humans; Male; Molecular Targeted Therapy; Rats; Tissue Distribution

Maleimide-conjugating closo-dodecaborate sodium form 5c (MID) synthesized by the nucleophilic ring-opening reaction of closo-dodecaborate-1,4-dioxane complex 2 with tetrabutylammonium (TBA) azide was found to conjugate to free SH of cysteine and lysine residues in BSA under physiological conditions, forming highly boronated BSA that showed high and selective accumulation in tumor and significant tumor growth inhibition in colon 26 tumor-bearing mice subjected to thermal neutron irradiation.

Topics: Animals; Boron; Boron Compounds; Boron Neutron Capture Therapy; Cell Line; Cysteine; Drug Carriers; Female; Lysine; Maleimides; Mice; Mice, Inbred BALB C; Models, Molecular; Neoplasms; Serum Albumin, Bovine

closo-Dodecaborate-encapsulating liposomes were developed as boron delivery vehicles for neutron capture therapy. The use of spermidinium as a counter cation of closo-dodecaborates was essential not only for the preparation of high boron content liposome solutions but also for efficient boron delivery to tumors.

Topics: Animals; Antineoplastic Agents; Boron; Boron Compounds; Boron Neutron Capture Therapy; Cell Line, Tumor; Cell Survival; Female; Liposomes; Mice, Inbred BALB C; Neoplasms; Tumor Burden

The fluorescence-labeled closo-dodecaborane lipid (FL-SBL) was synthesized from (S)-(+)-1,2-isopropylideneglycerol as a chiral starting material. FL-SBL was readily accumulated into the PEGylated DSPC liposomes prepared from DSPC, CH, and DSPE-PEG-OMe by the post insertion protocol. The boron concentrations and the fluorescent intensities of the FL-SBL-labeled DSPC liposomes increased with the increase of the additive FL-SBL, and the maximum emission wavelength of the liposomes appeared at 531 nm. A preliminary in vivo imaging study of tumor-bearing mice revealed that the FL-SBL-labeled DSPC liposomes were delivered to the tumor tissue but not distributed to hypoxic regions.

Topics: Animals; Boron; Boron Compounds; Drug Delivery Systems; Female; Fluorescence; Liposomes; Mice; Neoplasms; Oxadiazoles; Phosphatidylcholines; Phosphatidylethanolamines; Polyethylene Glycols; Stearates; Tissue Distribution

Closo-dodecaborate lipid liposomes were developed as new vehicles for boron delivery system (BDS) of neutron capture therapy. The current approach is unique because the liposome shell itself possesses cytocidal potential in combination with neutron irradiation. The liposomes composed of closo-dodecaborate lipids DSBL and DPBL displayed high cytotoxicity with thermal neutron irradiation. The closo-dodecaborate lipid liposomes were taken up into the cytoplasm by endocytosis without degradation of the liposomes. Boron concentration of 22.7 ppm in tumor was achieved by injection with DSBL-25% PEG liposomes at 20mg B/kg. Promising BNCT effects were observed in the mice injected with DSBL-25% PEG liposomes: the tumor growth was significantly suppressed after thermal neutron irradiation (1.8 x 10(12)neutrons/cm(2)).

Topics: Animals; Boron; Boron Compounds; Boron Neutron Capture Therapy; Cell Line, Tumor; Drug Delivery Systems; Female; Lipids; Liposomes; Mice; Mice, Inbred BALB C; Microscopy, Electron, Transmission; Neoplasms; Radiopharmaceuticals; Tissue Distribution; Tumor Burden