| 摘要 |
Cancer cells that exhibit low levels of NMNAT are refractory to tiazofurin therapy, and diagnostic methods for assessing NMNAT levels, particularly human NMNAT2, are described, as are compositions and methods for enhancing cytotoxicity towards tiazofurin (2-beta-D-ribofuranosylthiazole4-carboxamide), a pro-drug metabolized by nicotinamide mononucleotide adenylyltransferase (NMNAT) to TAD (thiazole-4-carboxamide adenine dinucleotide). Examples of such compositions include gene delivery vehicles that provide for enhanced NMNAT expression in transfected cells, as well as targeted drug delivery compositions that include tiazofurin encapsulated in folate-tethered nanoparticles. This approach shows that increasing NMNAT levels, particularly hNMNAT2 levels, enhances tiazofurin-mediated cell killing, which has relevance in the treatment of various disease, including various cancers and infectious diseases. |
