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.
MeSH terms
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Caspases / metabolism
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Chlorambucil / chemistry
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Chlorambucil / pharmacology*
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Coloring Agents / chemistry
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Coloring Agents / pharmacology*
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Dose-Response Relationship, Drug
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Drug Delivery Systems
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Drug Screening Assays, Antitumor
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Drug Therapy, Combination
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Glutathione / metabolism
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Humans
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Mitochondria / drug effects*
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Mitochondria / metabolism
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Mitochondria / pathology*
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Molecular Structure
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Molecular Targeted Therapy*
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Prodrugs / chemistry
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Prodrugs / pharmacology*
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Coloring Agents
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Prodrugs
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Chlorambucil
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Caspases
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Glutathione