title: Folate-based near-infrared fluorescent theranostic gemcitabine delivery.
abstract: A series of heptamethine cyanine (1-3) derivatives bearing a carbamate ethyl disulfide group and gemcitabine, an anticancer drug, have been newly synthesized. Their disulfide bonds are readily cleaved by various thiols including glutathione, to result in a subsequent decomposition of the carbamate into amine followed by release of the active gemcitabine, which can be monitored by the fluorescence changes. In the biological experiment, prodrug 1 is preferentially up-taken by folate-positive KB cells over folate-negative A549 cells via receptor-mediated endocytosis to release gemcitabine causing cell death and to emit fluorescence in endoplasmic reticulum. Moreover, it is selectively accumulated in the KB cells which were treated to mice by dorsal subcutaneous injection. This drug delivery system is a new theranostic agent, wherein both therapeutic effect and drug uptake can be easily monitored at the subcellular level, by in vivo and in vitro fluorescence imaging.
authors.affiliation: Department of Chemistry, Korea University, Seoul 136-701, Korea.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Yang
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Lee
authors.forename: Hyun Mi
authors.initials: HM
authors.lastname: Jeon
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Han
authors.forename: Nayoung
authors.initials: N
authors.lastname: Park
authors.forename: Yanxia
authors.initials: Y
authors.lastname: He
authors.forename: Hyunseung
authors.initials: H
authors.lastname: Lee
authors.forename: Kwan Soo
authors.initials: KS
authors.lastname: Hong
authors.forename: Chulhun
authors.initials: C
authors.lastname: Kang
authors.forename: Jong Seung
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002232:Carbocyanines / Q000737:chemistry*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000737:chemistry*; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007624:KB Cells; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D061848:Optical Imaging; D013438:Sulfhydryl Compounds / Q000737:chemistry; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D002232:Carbocyanines; D004337:Drug Carriers; D005456:Fluorescent Dyes; D013438:Sulfhydryl Compounds; C501744:indotricarbocyanine; D003841:Deoxycytidine; D005492:Folic Acid; D000093542:Gemcitabine