Targeted combinational therapy inducing mitochondrial dysfunction

Weon Sup Shin; Soon Ki Park; Peter Verwilst; Seyoung Koo; Joung Hae Lee; Sung-Gil Chi; Jong Seung Kim

doi:10.1039/c6cc08977a

Targeted combinational therapy inducing mitochondrial dysfunction

Weon Sup Shin, Soon Ki Park, Peter Verwilst, Seyoung Koo, Joung Hae Lee, Sung-Gil Chi, Jong Seung Kim

Research output: Contribution to journal › Article › peer-review

25 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1281-1284
Number of pages	4
Journal	Chemical Communications
Volume	53
Issue number	7
DOIs	https://doi.org/10.1039/c6cc08977a
Publication status	Published - 2017

ASJC Scopus subject areas

Catalysis
Electronic, Optical and Magnetic Materials
Ceramics and Composites
Chemistry(all)
Surfaces, Coatings and Films
Metals and Alloys
Materials Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1039/c6cc08977a

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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.",

author = "Shin, {Weon Sup} and Park, {Soon Ki} and Peter Verwilst and Seyoung Koo and Lee, {Joung Hae} and Sung-Gil Chi and Kim, {Jong Seung}",

note = "Funding Information: This work was supported by the Ministry of Science, ICT and Future Planning (MSIP) of the National Research Foundation of Korea (No. 2009-0081566 for JSK and NRF-20158A2A1A01005389 for SGC). This research was supported by the Korea Research Fellowship Program funded by the Ministry of Science, ICT and Future Planning through the National Research Foundation of Korea (2016H1D3A1938052 for PV). Publisher Copyright: {\textcopyright} The Royal Society of Chemistry. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2017",

doi = "10.1039/c6cc08977a",

language = "English",

volume = "53",

pages = "1281--1284",

journal = "Chemical Communications",

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publisher = "Royal Society of Chemistry",

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T1 - Targeted combinational therapy inducing mitochondrial dysfunction

AU - Shin, Weon Sup

AU - Park, Soon Ki

AU - Verwilst, Peter

AU - Koo, Seyoung

AU - Lee, Joung Hae

AU - Chi, Sung-Gil

AU - Kim, Jong Seung

N1 - Funding Information: This work was supported by the Ministry of Science, ICT and Future Planning (MSIP) of the National Research Foundation of Korea (No. 2009-0081566 for JSK and NRF-20158A2A1A01005389 for SGC). This research was supported by the Korea Research Fellowship Program funded by the Ministry of Science, ICT and Future Planning through the National Research Foundation of Korea (2016H1D3A1938052 for PV). Publisher Copyright: © The Royal Society of Chemistry. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

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SP - 1281

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JO - Chemical Communications

JF - Chemical Communications

IS - 7

ER -

Targeted combinational therapy inducing mitochondrial dysfunction

Abstract

ASJC Scopus subject areas

UN SDGs

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