1. Interaction of N-hydroxy(sulfo) succinimide active esters with the reduced folate/methotrexate transport system from human leukemic CCRF-CEM cells
G Jansen, G R Westerhof, G Rijksen, J H Schornagel Biochim Biophys Acta. 1989 Nov 3;985(3):266-70. doi: 10.1016/0005-2736(89)90411-2.
The membrane impermeant protein cross-linker 3,3'-dithiobissulfosuccinimidyl propionate (DTSSP) is a well-known inhibitor of human erythrocyte band 3-mediated inorganic anion transport. We observed that DTSSP is also a potent inhibitor of reduced folate/methotrexate transport in human CCRF-CEM leukemia cells. An interaction of DTSSP with the reduced folate/MTX is substantiated by findings that: (a) like MTX transport itself, the concentration of DTSSP required for half-maximal inhibition of [3H]methotrexate transport varied substantially with the anionic composition of the external medium. In a saline buffer and an anion-deficient buffer the I50 values were 7 and 1 microM, respectively; (b) saturation of the carrier with 1-5 microM methotrexate completely protected the transport system from interaction by DTSSP; (c) methotrexate transport activity in DTSSP-treated cells could be restored after cleavage of the disulfide bond in DTSSP under mild reducing conditions; and (d) pretreatment of cells with DTSSP reduced the incorporation of [3H]methotrexate after labeling with an N-hydroxysuccinimide ester of [3H]methotrexate (NHS-MTX), another potent inhibitor of methotrexate transport. Comparison of DTSSP- and NHS-MTX-induced inhibition of methotrexate transport showed that DTSSP inhibition, in contrast to NHS-MTX inhibition, was (a) less potent, (b) dependent on buffer conditions, (c) reversible by reducing agents, and (d) required only a very low molar ratio of methotrexate over DTSSP to afford maximal protection.
2. Progress and Current Trends in the Synthesis of Novel Polymers with Enhanced Mucoadhesive Properties
Ruairí P Brannigan, Vitaliy V Khutoryanskiy Macromol Biosci. 2019 Oct;19(10):e1900194. doi: 10.1002/mabi.201900194. Epub 2019 Jul 30.
Mucoadhesion is defined as the adherence of a synthetic or natural polymer to a mucosal membrane via physical or chemical interactions. Mucoadhesive materials are widely used to develop dosage forms for transmucosal drug delivery via ocular, nasal, esophageal, oral, vaginal, rectal, and intravesical routes of administration. This review will discuss some of the most prominent and recent synthetic methodologies employed to modify polymeric materials in order to enhance their mucoadhesive properties. This includes chemical conjugation of polymers with molecules bearing thiol-, catechol-, boronate-, acrylate-, methacrylate-, maleimide-, and N-hydroxy(sulfo)succinimide ester- groups.
3. Principle and clinical usefulness of the infrared fluorescence endoscopy
Susumu Ito, Naoki Muguruma, Tetsuo Kimura, Hiromi Yano, Yoshitaka Imoto, Koichi Okamoto, Masako Kaji, Shigeki Sano, Yoshimitsu Nagao J Med Invest. 2006 Feb;53(1-2):1-8. doi: 10.2152/jmi.53.1.
Since there is no infrared fluorescence materials in the living body, infrared fluorescence labeling materials are very useful for making a diagnosis of a micro cancer. We have developed an infrared fluorescence endoscope (IRFE) and indocyanin green (ICG)-derivative as infrared fluorescence labeling materials to evaluate gastrointestinal neoplastic lesions. The study aims were to apply an IRFE and to demonstrate its usefulness in detecting cancerous tissue using an antibody coupled with ICG-derivative. IRFE consisted of an infrared endoscope equipped with excitation (710-790 nm) and barrier (810-920 nm) filters and an intensified CCD camera. We have developed ICG N-hydroxy sulfo succinimide ester (ICG-sulfo-OSu) and 3-ICG-acyl-1, 3-thiazolidine-2-thione (ICG-ATT) as an infrared fluorescent-labeling reagent. ICG-derivative-labeled mouse anti-human carcinoembryonic antigen (CEA) antibody and MUC1 antibody were employed in this study. Moreover, we examined the ability of a reinforcement agent, octylglucoside, to intensity fluorescence from the labeled antibody. Biopsy specimens of gastric cancer were stained with anti-CEA antibody by the avidin-biotinylated peroxidase complex method. Among the positive specimens, freshly resected stomach from three cases were used for the infrared (IR) imaging analysis. The incubation of freshly resected stomach specimens with ICG-anti-CEA antibody-complex resulted in positive staining of the tumor sites by IRFE, and the IR fluorescent images correlated well with the tumor sites. The immunohistochemical studies suggested that the intensity of IR fluorescence of ICG-ATT-MUC1 was stronger than that of ICG-sulfo-OSu. In tumor sections, the reinforcement agent intensified fluorescence, ever at low antibody concentrations. Therefore, we conclude that an anti-CEA (and/or MUC1) antibody with affinity for cancerous lesions and labeled with ICG-derivative can be imaged with this IRFE. Specific antibodies tagged with ICG-derivative with the reinforcement agent can label cancer cells and generate a strong enough fluorescent signal to detect small cancers when examined with an IR fluorescence endoscope.
