title: Gemcitabine-coumarin-biotin conjugates: a target specific theranostic anticancer prodrug.
abstract: We present here, the design, synthesis, spectroscopic characterization, and in vitro biological assessment of a gemcitabine-coumarin-biotin conjugate (5). Probe 5 is a multifunctional molecule composed of a thiol-specific cleavable disulfide bond, a coumarin moiety as a fluorescent reporter, gemcitabine (GMC) as a model active drug, and biotin as a cancer-targeting unit. Upon addition of free thiols that are relatively abundant in tumor cells, disulfide bond cleavage occurs as well as active drug GMC release and concomitantly fluorescence intensity increases. Confocal microscopic experiments reveal that 5 is preferentially taken up by A549 cells rather than WI38 cells. Fluorescence-based colocalization studies using lysosome- and endoplasmic reticulum-selective dyes suggest that thiol-induced disulfide cleavage of 5 occur in the lysosome possibly via receptor-mediated endocytosis. The present drug delivery system is a new theranostic agent, wherein both a therapeutic effect and drug uptake can be readily monitored at the subcellular level by two photon fluorescence imaging.
authors: Department of Chemistry, Korea University, Seoul, 136-701, Korea.
authors: Sukhendu
authors: S
authors: Maiti
authors: Nayoung
authors: N
authors: Park
authors: Ji Hye
authors: JH
authors: Han
authors: Hyun Mi
authors: HM
authors: Jeon
authors: Jae Hong
authors: JH
authors: Lee
authors: Sankarprasad
authors: S
authors: Bhuniya
authors: Chulhun
authors: C
authors: Kang
authors: Jong Seung
authors: JS
authors: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D001710:Biotin / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000737:chemistry; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D005456:Fluorescent Dyes; D011355:Prodrugs; D013438:Sulfhydryl Compounds; D003841:Deoxycytidine; D001710:Biotin; C030123:coumarin; D000093542:Gemcitabine