Click and photo-unclick chemistry of aminoacrylate for visible light-triggered drug release

Bio, Moses; Nkepang, Gregory; You, Youngjae

doi:10.1039/c2cc32373g

Cited by 90 publications

(83 citation statements)

References 16 publications

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“…With a ratiometric comparison to the essentially unchanged acceptor emission, singlet oxygen generation ability of the photosensitizer can be assessed. The You group investigated 16 a similarly designed system for its drug release potential. However, to the best of our knowledge, explicit reactionbased modulation of EET 21 toward singlet oxygen-dependent ratiometric self-activity sensing of a photosensitizer has not been reported before.…”

mentioning

confidence: 99%

Toward Singlet Oxygen Delivery at a Measured Rate: A Self-Reporting Photosensitizer

Erbaş-Çakmak

Akkaya

2014

Org. Lett.

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A Bodipy-based energy transfer cassette with a singlet oxygen reactive linker between the donor and acceptor modules has an interesting emergent property, if the acceptor module is also a photosensitizer. Singlet oxygen produced by the photosensitizer reacts rapidly with the molecule itself to liberate the energy donor, resulting in an enhanced fluorescence emission. The result is a self-reporting photosensitizer providing an assessment of the singlet oxygen production rate under the operational conditions. S ensing analytes in solution is highly important both for the elucidation of the processes they are involved in and/or for determining therapeutic/diagnostic approaches in diseases where corresponding analytes are markers for various biological anomalies. 1,2 Apart from using analyte responsive molecules as reporters, activatable therapeutic systems have been developed as well, where the disease related parameter is used to initiate a chemical/physical transformation in the therapeutic agent to alter its activity. Activatable photosensitizers are one of such therapeutics with a modulated activatability property. 3−8 Exchange of ideas between the fields of therapeutic design and molecular sensors is expected to yield great improvements in personalized treatment and diagnostics. However, one of the main problems not addressed so far in this overlap area, is the inadequacy of measuring the effect of any therapeutics directly. Rather, the biological effect is analyzed on a cellular level. For the photosensitizers, the effect of light, oxygen concentration, cell penetration, and dark-toxicity determines the overall effect of the photosensitizer on the cell; 9,10 hence, one has to be cautious in speaking about the efficiency of singlet oxygen production of a photosensitizer in a cell-culture experiment since the observed outcome is a cumulative result, namely cell death.In this work, we address the issue of direct monitoring of photosensitizer activity with the use of a singlet oxygen ( 1 O 2 ) labile linker between the fluorophore and a photosensitizer, where the former is an electronic energy transfer (EET) donor and the latter being an EET acceptor (Figure 1, BOD 2). The rationale behind the design is such that EET from the fluorophore (FL, blue module in Figure 1) to the photosensitizer (PS, green module on BOD 2) quenches the emission of the FL to a great extent. PS and FL are attached to one another with (Z)-1,2-bis(alkylthio)ethene bridge due to the fact that 1 O 2 susceptibility of this electron-rich olefinic linker is extensively exploited by us and others. 11−16 According to the design, 1 O 2 generated by the PS upon irradiation with red light is to act on the molecule itself and cleave the linker, liberating the fluorophore as a consequence. Fluorescence of the free FL is reinstated which is the reporter

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confidence: 99%

Toward Singlet Oxygen Delivery at a Measured Rate: A Self-Reporting Photosensitizer

Erbaş-Çakmak

Akkaya

2014

Org. Lett.

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“…It is proposed that this fiber optics-guided delivery of oxygen and PSs could be applied to hypoxic conditions. Activation of prodrugs by an SO-cleavable linker was demonstrated by Jiang et al [48] and Bio et al [49]. One of the key requirements of prodrugs is the release of the parent drug without any modification to drug structure.…”

Section: Laser On Laser Offmentioning

confidence: 99%

“…Irradiation cleaved the SO-labile linkers releasing free drugs. Bio et al developed a new type of SO-cleavable linker (aminoacrylate) which overcame a number of the limitations of the previous SO-cleavable linkers, such asa limited number of SO-cleavable linkers (e.g., vinyl dithioether, vinyl diether), the lack of facile synthetic approach for the cleavable linkers, andthe regeneration of the parent drug [49]. The amino acrylate linker can be synthesized by a click reaction and can be cleaved by an SO mechanismupon irradiation with a PS; this reaction is termed "click and photo-unclick chemistry" (Scheme 4b).…”

Section: Laser On Laser Offmentioning

confidence: 99%

Emerging Strategies for Controlling Drug Release by Using Visible/Near IR Light

Bio¹,

You²

2013

Med Chem

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Effective drug delivery systems require controlled drug release at the target cancer cell. While strategies for targeting tumors have been extensively studied, a better understanding of the necessary technology for controlling the spatiotemporal release of a drug is still needed. It has been established that the use of light can be a unique tool for controlling drug release. While UV light can be used for the release of biologically active, caged (deactivated) compounds, clinical application is restricted because of its limited ability to penetrate tissues as well as its cytotoxicity. Recently, the use of both tissue-penetrable visible and near IR have shown promise to overcome these limitations. In this short review, we introduce new smart strategies to convert such low energy light to a tissue-penetrable stimulus for both actively and remotely controlling drug release.

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“…In fact, the cleavage of an aminoacrylate linker by the combination of 690 nm and dithiaporphyrin PS was verified in our previous experiments. 16 On the basis of the photounclick chemistry, here we first successfully demonstrate the visible light-triggered PDs of anticancer compounds. In particular, we prepared a double activatable PD system to prove the concept of dPS, which could be further engineered to improve specificity of activation.…”

mentioning

confidence: 99%

“…16 Because singlet oxygen can be generated by the combination of visible/near IR light (400−800 nm) and a corresponding PS, an aminoacrylate linker can be cleaved by such low energy light via singlet oxygen. In fact, the cleavage of an aminoacrylate linker by the combination of 690 nm and dithiaporphyrin PS was verified in our previous experiments.…”

mentioning

confidence: 99%

Visible Light Controlled Release of Anticancer Drug through Double Activation of Prodrug

Hossion

Bio

Nkepang

et al. 2012

ACS Med. Chem. Lett.

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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/cm 2 ) 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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Click and photo-unclick chemistry of aminoacrylate for visible light-triggered drug release

Cited by 90 publications

References 16 publications

Toward Singlet Oxygen Delivery at a Measured Rate: A Self-Reporting Photosensitizer

Toward Singlet Oxygen Delivery at a Measured Rate: A Self-Reporting Photosensitizer

Emerging Strategies for Controlling Drug Release by Using Visible/Near IR Light

Visible Light Controlled Release of Anticancer Drug through Double Activation of Prodrug

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