Visible light controlled release of anticancer drug through double activation of prodrug

Abugafar M.L. Hossion; Moses Bio; Gregory Nkepang; Samuel G. Awuah; Youngjae You

doi:10.1021/ml3003617

Visible light controlled release of anticancer drug through double activation of prodrug

Abugafar M.L. Hossion, Moses Bio, Gregory Nkepang, Samuel G. Awuah, Youngjae You

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

85 Scopus citations

Abstract

We designed and synthesized a novel double activatable prodrug system (drug-linker-deactivated photosensitizer), containing a photocleavable aminoacrylate-linker and a deactivated photosensitizer, to achieve the spatiotemporally controlled release of parent drugs using visible light. Three prodrugs of CA-4, SN-38, and coumarin were prepared to demonstrate the activation of deactivated photosensitizer by cellular esterase and the release of parent drugs by visible light (540 nm) via photounclick chemistry. Among these prodrugs, nontoxic coumarin prodrug was used to quantify the release of parent drug in live cells. About 99% coumarin was released from the coumarin prodrug after 24 h of incubation with MCF-7 cells followed by irradiation with low intensity visible light (8 mW/cm²) for 30 min. Less toxic prodrugs of CA-4 and SN-38 killed cancer cells as effectively as free drugs after the double activation.

Original language	English
Pages (from-to)	124-127
Number of pages	4
Journal	ACS Medicinal Chemistry Letters
Volume	4
Issue number	1
DOIs	https://doi.org/10.1021/ml3003617
State	Published - Jan 10 2013

Keywords

Prodrug
aminoacrylate
anticancer drug
photosensitizer
photounclick
visible/near IR

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

UN SDGs

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

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10.1021/ml3003617

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title = "Visible light controlled release of anticancer drug through double activation of prodrug",

abstract = "We designed and synthesized a novel double activatable prodrug system (drug-linker-deactivated photosensitizer), containing a photocleavable aminoacrylate-linker and a deactivated photosensitizer, to achieve the spatiotemporally controlled release of parent drugs using visible light. Three prodrugs of CA-4, SN-38, and coumarin were prepared to demonstrate the activation of deactivated photosensitizer by cellular esterase and the release of parent drugs by visible light (540 nm) via photounclick chemistry. Among these prodrugs, nontoxic coumarin prodrug was used to quantify the release of parent drug in live cells. About 99% coumarin was released from the coumarin prodrug after 24 h of incubation with MCF-7 cells followed by irradiation with low intensity visible light (8 mW/cm2) for 30 min. Less toxic prodrugs of CA-4 and SN-38 killed cancer cells as effectively as free drugs after the double activation.",

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AU - Hossion, Abugafar M.L.

AU - Bio, Moses

AU - Nkepang, Gregory

AU - Awuah, Samuel G.

AU - You, Youngjae

PY - 2013/1/10

Y1 - 2013/1/10

N2 - We designed and synthesized a novel double activatable prodrug system (drug-linker-deactivated photosensitizer), containing a photocleavable aminoacrylate-linker and a deactivated photosensitizer, to achieve the spatiotemporally controlled release of parent drugs using visible light. Three prodrugs of CA-4, SN-38, and coumarin were prepared to demonstrate the activation of deactivated photosensitizer by cellular esterase and the release of parent drugs by visible light (540 nm) via photounclick chemistry. Among these prodrugs, nontoxic coumarin prodrug was used to quantify the release of parent drug in live cells. About 99% coumarin was released from the coumarin prodrug after 24 h of incubation with MCF-7 cells followed by irradiation with low intensity visible light (8 mW/cm2) for 30 min. Less toxic prodrugs of CA-4 and SN-38 killed cancer cells as effectively as free drugs after the double activation.

AB - We designed and synthesized a novel double activatable prodrug system (drug-linker-deactivated photosensitizer), containing a photocleavable aminoacrylate-linker and a deactivated photosensitizer, to achieve the spatiotemporally controlled release of parent drugs using visible light. Three prodrugs of CA-4, SN-38, and coumarin were prepared to demonstrate the activation of deactivated photosensitizer by cellular esterase and the release of parent drugs by visible light (540 nm) via photounclick chemistry. Among these prodrugs, nontoxic coumarin prodrug was used to quantify the release of parent drug in live cells. About 99% coumarin was released from the coumarin prodrug after 24 h of incubation with MCF-7 cells followed by irradiation with low intensity visible light (8 mW/cm2) for 30 min. Less toxic prodrugs of CA-4 and SN-38 killed cancer cells as effectively as free drugs after the double activation.

KW - Prodrug

KW - aminoacrylate

KW - anticancer drug

KW - photosensitizer

KW - photounclick

KW - visible/near IR

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JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 1

ER -

Visible light controlled release of anticancer drug through double activation of prodrug

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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