title: Targeted combinational therapy inducing mitochondrial dysfunction.
abstract: We report on a mitochondria-specific combinational theranostic agent, 1. This system contains a chlorambucil prodrug and an aggregation induced emission dye. In addition, compound 1 bears both an intracellular thiol-triggered moiety and a mitochondria targeting unit (triphenylphosphonium). Glutathione (GSH) is the most abundant thiol and its concentrations are significantly higher in a great number of cancer cell lines, compared to normal cells. The GSH-induced prodrug 1 upon activation releases chlorambucil and exhibits mitochondria targeted aggregation induced emission (AIE) fluorescence, resulting in cell apoptosis via the caspase pathway due to mitochondrial dysfunction.
authors.affiliation: Department of Chemistry, Korea University, Seoul 02841, Korea. jongskim@korea.ac.kr.
authors.forename: Weon Sup
authors.initials: WS
authors.lastname: Shin
authors.affiliation: Department of Life Sciences, Korea University, Seoul 02841, Korea. chi6302@korea.ac.kr.
authors.forename: Soon Ki
authors.initials: SK
authors.lastname: Park
authors.affiliation: Department of Chemistry, Korea University, Seoul 02841, Korea. jongskim@korea.ac.kr.
authors.forename: Peter
authors.identifier: http://orcid.org/0000-0002-4673-2050
authors.initials: P
authors.lastname: Verwilst
authors.affiliation: Department of Chemistry, Korea University, Seoul 02841, Korea. jongskim@korea.ac.kr.
authors.forename: Seyoung
authors.initials: S
authors.lastname: Koo
authors.affiliation: Korea Research Institute of Standards and Science, Daejeon 305-600, Korea.
authors.forename: Joung Hae
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Korea University, Seoul 02841, Korea. chi6302@korea.ac.kr.
authors.forename: Sung-Gil
authors.initials: SG
authors.lastname: Chi
authors.affiliation: Department of Chemistry, Korea University, Seoul 02841, Korea. jongskim@korea.ac.kr.
authors.forename: Jong Seung
authors.identifier: http://orcid.org/0000-0003-3477-1172
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002699:Chlorambucil / Q000737:chemistry / Q000494:pharmacology*; D004396:Coloring Agents / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D004359:Drug Therapy, Combination; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004396:Coloring Agents; D011355:Prodrugs; D002699:Chlorambucil; D020169:Caspases; D005978:Glutathione