Intracellular Modulation of Excited‐State Dynamics in a Chromophore Dyad: Differential Enhancement of Photocytotoxicity Targeting Cancer Cells

Kölemen, Safacan; Işık, Murat; Kim, Gyoung Mi; Kim, Dabin; Geng, Hao; Büyüktemiz, Muhammed; Karataş, Tuğçe; Zhang, Xianfu; Dede, Yavuz; Yoon, Juyoung; Akkaya, Engin U.

doi:10.1002/anie.201411962

Cited by 148 publications

(104 citation statements)

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“…This feature blocks formation of degenerate HOMOs and LUMOs and thus suppresses formation of the DS-TR state and consequent singlet oxygen generation. [50] GSH in cancer cells reacts with the styryl double bond, disrupting the extended π-conjugation and isolating a methylpyridinium (MP) moiety from the orthogonal BODIPY dimer. Upon photoexcitation of the GSH adduct (5-GSH), through-space charge transfer takes place from BOD1 to electron-deficient MP, in which BOD2 behaves like an orthogonal spacer (Figure 7a).…”

Section: Higher Intracellular Gsh Concentrations In Cancer Cells Actimentioning

confidence: 99%

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Activatable Photosensitizers: Agents for Selective Photodynamic Therapy

Kölemen

Yoon

et al. 2016

Adv Funct Materials

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427

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Recent developments in the design of bifunctional and activatable photo sensitizers rejuvenate the aging field of photodynamic sensitization and photodynamic therapy. While systematic studies have uncovered new dyes that can serve as potential photosensitizers, the most promising results have come from studies aimed at gaining precise control over the location and rate of cytotoxic singlet oxygen generation. As a consequence, higher selectivities and efficiencies in photodynamic treatment protocols are now within reach. This feature article highlights the variety of approaches that have been pur sued to improve photodynamic therapy and to transform simple photosensi tizers into smarter theranostic agents.

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Section: Higher Intracellular Gsh Concentrations In Cancer Cells Actimentioning

confidence: 99%

“…c) Survival rates of healthy cells (NIH 3T3, WI38 VA13) and of cancer cells (HeLa, SK Hep 1) which were incubated with (5) or (5r). Reproduced with permission [50]. Copyright 2015, John Wiley and Sons.…”

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confidence: 99%

Activatable Photosensitizers: Agents for Selective Photodynamic Therapy

Kölemen

Yoon

et al. 2016

Adv Funct Materials

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427

325

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“…This less than 300-nm radius, being less than a cellular length, indicates that an active photosensitizer in or at a target cell will have minimal effect on adjacent cells. Previous investigations of switchable photosensitizers by various groups have used a pH-activatable rubyrin derivative (13), a quenchertethered Si(IV) phthalocyanine (14) and pyropheophorbide (15), and various boron-dipyrromethene (BODIPY) dye-based scaffolds (16)(17)(18). Solvent microenvironment has been used to selectively photooxidize protein (19) and cellular targets (17), but only using intramolecular FRET quenching or solvent polarity effects on photoelectron transfer in BODIPY monomers or covalently linked dimers.…”

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confidence: 99%

Detergent-induced self-assembly and controllable photosensitizer activity of diester phenylene ethynylenes

Donabedian

Creyer

Monge

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Photodynamic therapy, in which malignant tissue is killed by targeted light exposure following administration of a photosensitizer, can be a valuable treatment modality but currently relies on passive transport and local irradiation to avoid off-target oxidation. We present a system of excited-state control for truly local delivery of singlet oxygen. An anionic phenylene ethynylene oligomer is initially quenched by water, producing minimal fluorescence and no measurable singlet oxygen generation. When presented with a binding partner, in this case an oppositely charged surfactant, changes in solvent microenvironment result in fluorescence unquenching, restoration of intersystem crossing to the triplet state, and singlet oxygen generation, as assayed by transient absorption spectroscopy and chemical trapping. This solvation-controlled photosensitizer model has possible applications as a theranostic agent for, for example, amyloid diseases.photosensitizer | self-assembly | conjugated oligomers | photodynamic therapy | excited states G eneration of reactive oxygen species as a product of photoexcited electronic states in organic molecules can be a useful tool in a variety of applications. The possibilities of spatially localized generation of reactive oxygen species (ROS) in response to irradiation are only just beginning to be explored, despite the more than 100-y history of phototherapy in modern medicine (1), and are already in the clinic in the form of photodynamic therapy (PDT) for cancers of the skin, esophagus, and organ linings, actinic keratosis, and acne (2, 3). Photodynamic destruction of pathogenic bacteria, viruses, and fungi is also under investigation for antibiowarfare applications, passive sanitization of hospital surfaces under room light, and active sanitization of medical devices such as catheters (4-8). A major drawback of systemically dosed PDT photosensitizers, which are primarily porphyrins or their prodrugs (9), is their accumulation in the skin and eyes leading to long-lasting (weeks to months) posttherapeutic photosensitivity (10). Generation of ROS outside the target area can have multiple deleterious effects by overwhelming endogenous ROS-dependent signaling cascades (11). A solution to these issues would be a localized photosensitizer whose ROS-generating properties can be controllably activated, for example, in response to the binding to a target.The motivation of the current study is to develop a tool for local delivery of singlet oxygen using binding and self-assemblymediated control of excited states. Under intra-or intercellular conditions, 99% of singlet oxygen cannot travel more than 300 nm from the site of its generation before it decays through the transfer of its electronic energy to vibrational modes of water (12); the presence of redox sites will reduce this effective distance further. This less than 300-nm radius, being less than a cellular length, indicates that an active photosensitizer in or at a target cell will have minimal effect on adjacent cells. Previous investiga...

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“…In addition, the versatility of the chemistry of BODIPY derivatives has led to the employment of these molecules more and more frequently in the development of novel strategies towards the improvement of PDT. [17] Based on these considerations,wedesigned abifunctional compound to meet the requirements for enhanced fractional photodynamic therapy.T he operation principle for the generation of singlet oxygen is shown in Figure 1. When excited at l = 650 nm, the upper dye molecule in the figure (Pyr 6)isexpected to generate singlet oxygen, and some of it will be "stored" in the form of a2 -pyridone endoperoxide (EPO 7).…”

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confidence: 99%

A Bifunctional Photosensitizer for Enhanced Fractional Photodynamic Therapy: Singlet Oxygen Generation in the Presence and Absence of Light

et al. 2016

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The photosensitized generation of singlet oxygen within tumor tissues during photodynamic therapy( PDT) is self-limiting,a st he already lowo xygen concentrations within tumors is further diminished during the process.I nc ertain applications,t om inimize photoinduced hypoxia the light is introduced intermittently (fractional PDT) to allowt ime for the replenishment of cellular oxygen. This condition extends the time required for effective therapy. Herein, we demonstrated that ap hotosensitizer with an additional 2-pyridone module for trapping singlet oxygen would be useful in fractional PDT.T hus,i nt he light cycle,t he endoperoxide of 2-pyridone is generated along with singlet oxygen. In the dark cycle,t he endoperoxideu ndergoes thermal cycloreversion to produce singlet oxygen, regenerating the 2-pyridone module. As aresult, the photodynamic process can continue in the dark as well as in the light cycles.Cell-culture studies validated this working principle in vitro.

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Intracellular Modulation of Excited‐State Dynamics in a Chromophore Dyad: Differential Enhancement of Photocytotoxicity Targeting Cancer Cells

Cited by 148 publications

References 31 publications

Activatable Photosensitizers: Agents for Selective Photodynamic Therapy

Activatable Photosensitizers: Agents for Selective Photodynamic Therapy

Detergent-induced self-assembly and controllable photosensitizer activity of diester phenylene ethynylenes

A Bifunctional Photosensitizer for Enhanced Fractional Photodynamic Therapy: Singlet Oxygen Generation in the Presence and Absence of Light

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