Beta-cyclodextrin/surface plasmon resonance detection system for sensing bitter-astringent taste intensity of green tea catechins.

To develop a methodology for creating a sensor with a receptor for specific taste substances, we focused on constructing a sensing system for the bitter-astringent taste intensity of green tea catechins: (-)-epigallocatechin-3-O-gallate (EGCg), (-)-epicatechin-3-O-gallate (ECg), (-)-epigallocatechin (EGC), and (-)-epicatechin (EC). (1)H NMR titration experiments revealed that beta-cyclodextrin was an adequate receptor for sensing the bitter-astringent taste intensity of catechins. A surface plasmon resonance (SPR) system immobilized beta-cyclodextrin indicated larger responses for the gallate-type catechins in comparison to the non-gallate-type catechins. These responses corresponded to the tendency of the bitter-astringent taste intensity of the catechins felt by humans. Furthermore, the SPR system detected the larger stability of the complex between the gallate-type catechins and beta-cyclodextrin, which was interpreted as the aftertaste produced in humans by the gallate-type catechins. These results demonstrate that the beta-cyclodextrin/SPR system can sense the bitter-astringent taste intensity of the green tea catechins similar to human gustation. The methodology presented in this study can be used as a basic strategy for developing taste sensors with specific receptor functions.

Applicability of the 2-nitroimidazole-sodium borocaptate-10B conjugate, TX-2060, as a 10B-carrier in boron neutron capture therapy.

BACKGROUND: It is difficult to deliver a therapeutic amount of 10B from conventional 10B-carriers for boron neutron capture therapy (BNCT) throughout the target tumors, especially into the intratumor hypoxic cells which have low uptake capacities. We evaluated the usefulness of 5 new 10B-compounds (TX-2041, TX-2042, TX-2058, TX-2059 and TX-2060) as 10B-carriers in BNCT. They are 2-nitroimidazole-sodium borocaptate-10B (BSH) conjugates, that is, hybrid compounds that have both a hypoxic tumor cell sensitizing unit under gamma-ray irradiation, 2-nitroimidazoles and a thermal neutron-sensitizing unit, BSH. MATERIALS AND METHODS: The 5 new compounds were administered to SCC VII tumor-bearing mice intraperitoneally. As a control, BSH was also administered in the same manner. Then, the 10B concentrations in the tumors and normal tissues were measured by gamma-ray spectrometry. Based on the data of the pharmacokinetics analyses, TX-2060 was chosen for a subsequent tumor-irradiation study. SCC VII tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells in the tumors, then treated with TX-2060 or BSH in the same manner as in the pharmacokinetics analyses. To obtain similar intratumor 10B concentrations during radiation exposure, irradiation with thermal neutrons or gamma-rays was started from 60 min after administration of the 10B-carrier. Right after irradiation, the tumors were excised, minced and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU-labelling (= quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. Meanwhile, the MN frequency in total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU. The clonogenic cell survival was also determined in mice given no BrdU. RESULTS: 10B distribution analyses in tumors, muscles, blood and liver indicated that TX-2060 has the most favorable characteristics for concentrating a sufficient amount of 10B in tumors and maintaining a high enough 10B concentration during irradiation. In addition, TX-2060 had a significantly stronger radio-sensitization effect with reactor thermal neutron beams than BSH on both total and Q cells in solid tumors. Further, TX-2060 clearly exhibited a radio-sensitization effect with gamma-rays, not only on total cells but also on Q and hypoxic tumor cells, which was not achieved by BSH. CONCLUSION: 10B-carrier, with a gamma-ray-sensitizing effect on tumor cells as well as the potential to keep 10B in tumors and sensitize tumor cells more markedly than conventional 10B-carriers, such as TX-2060, is a promising candidate for use in BNCT.