<i>Cis‐Trans</i>Photoisomerization of Stilbenes and Stilbene‐Like Molecules

Görner, Helmut; Kuhn, Hans

doi:10.1002/9780470133507.ch1

Cited by 57 publications

(82 citation statements)

References 546 publications

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“…7,8 The Z-isomer of CA4 is highly cytotoxic having a nanomolar LD 50 in the MTT assay whilst the corresponding E-isomers of combretastatins are usually less toxic by 2 or 3 orders of magnitude. 9 As with most stilbenes, 10 photoisomerization of combretastatins occurs on illumination within their UV absorption band (ca 320-340 nm) 11 and offers a route to photoactivation via E ⇌ Z isomerization that is independent of oxygen and therefore potentially useful in a wide range of tissues including hypoxic tumours. Whilst the optical transmission of tissues prevents the use of UV activation via usual one-photon absorption, an optical "window" in the spectra of tissues lies in the range of 600 -900 nm, 12 equivalent to red or near-infrared wavelengths, permitting 2-or 3-photon absorption and activation of the E-combretastatin at approximately 640 nm or 960 nm respectively.…”

Section: Introductionmentioning

confidence: 99%

Anticancer phototherapy using activation of E -combretastatins by two-photon–induced isomerization

et al. 2014

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Abstract. The photoisomerization of relatively non-toxic E-combretastatins to clinically active Z-isomers is shown to occur in solution through both one-and two-photon excitations at 340 and 625 nm respectively. The photoisomerization is also demonstrated to induce mammalian cell death by a two-photon absorption process at 625 nm. Unlike conventional photodynamic therapy (PDT), the mechanism of photoisomerization is oxygenindependent and active in hypoxic environments such as in tumors. The use of red or near-infrared light for twophoton excitation allows greater tissue penetration than conventional UV one-photon excitation. The results provide a baseline for the development of a novel phototherapy that overcomes non-discriminative systemic toxicity of Z-combretastatins and the limitations of PDT drugs that require the presence of oxygen to promote their activity, with the added benefits of 2-photon red or near-infrared (NIR) excitation for deeper tissue penetration.

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Section: Introductionmentioning

confidence: 99%

Anticancer phototherapy using activation of E -combretastatins by two-photon–induced isomerization

et al. 2014

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“…Fluorescence yields and lifetimes of E-isomers increase with solvent viscosity as the competing E→Z isomerization rate decreases. 6 Electronic excitation of fluorophores using two-photon excitation (2PE) is seen as an attractive method for biological imaging and cellular photochemistry 7 because of the transmission of near infrared light through tissue and readily available ultrafast Ti:sapphire lasers providing MHz 200 fs pulse trains. The concept of using 2PE to isomerise Ecombretastatins relates to other biological applications of multiphoton excitation such as in photodynamic therapy 8 where tissues are very much more transparent in the near-infrared region (700 -900 nm) than in the visible spectrum.…”

Section: Introductionmentioning

confidence: 99%

Fluorescence lifetime imaging of E-combretastatin uptake and distribution in live mammalian cells

Bisby

Botchway

Hadfield

et al. 2012

European Journal of Cancer

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To investigate within live mammalian cells the uptake and disposition of combretastatins, fluorescence lifetime imaging was used with two-photon excitation (2PE). Combretastatin A4 (CA4) and analogues are potential anticancer drugs due to their ability to inhibit angiogenesis. E(trans)-combretastatins are considerably less active than the Z(cis)-combretastatins proposed for clinical use. However the E-combretastatins exhibit stronger intrinsic fluorescence with quantum yields and lifetimes that depend markedly on solvent polarity and viscosity. It is proposed that 2PE in the red and near-infrared tissue window may allow in situ isomerization of Ecombretastatins to the more active Z-isomer, offering spatial and temporal control of drug activation and constitute a novel form of photodynamic therapy. In the present work we have characterised 2PE of E-CA4 and have used fluorescence lifetime imaging with 2PE to study uptake and intracellular disposition of E-CA4 and an analogue. The results show that these molecules accumulate rapidly in cells and are located mainly in lipidic environments such as lipid droplets. Within the droplets the local concentrations may be up to 2 orders of magnitude higher than that of the drug in the surrounding medium.

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“…It is a direct pro-drug activation without the need of the formation of a long-lived energy transferring triplet state and furthermore an oxygen-independent process. The photoisomerization process is reversible and depends on the wavelength used for excitation as it is commonly seen for stilbenes [123,124].…”

Section: Alternative Strategy For Two-photon Phototherapy (2p-pdt) Wimentioning

confidence: 99%

New Approaches to Photodynamic Therapy from Types I, II and III to Type IV Using One or More Photons

Scherer

Bisby²,

Botchway³

et al. 2017

ACAMC

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Photodynamic therapy (PDT) is an alternative cancer treatment to conventional surgery, radiotherapy and chemotherapy. It is based on activating a drug with light that triggers the generation of cytotoxic species that promote tumour cell killing. At present, PDT is mainly used in the treatment of wet age-related macular degeneration, for precancerous conditions of the skin (e.g. actinic keratosis) and in the palliative care of advanced cancers, for instance of the bladder or the oesophagus. Due to a lack of phase III clinical trials and limitations of light penetration to deeper lying tumours (in excess of 1 cm), PDT is still not used as a first line cancer treatment, which is surprising given the first clinical trials by Dougherty's group dating back to the 1970's. However research continues to demonstrate the potential benefits of PDT and the need to stimulate funding and uptake of clinical studies using next generation photosensitizers offering advanced targeted delivery, improved photodynamic dose combined with modern light delivery technologies. This review surveys the available PDT treatments and emerging novel developments in the field with a particular focus on two-photon techniques that are anticipated to improve the effectiveness of PDT in tissues at depth and on next generation drugs that work without the need of the presence of oxygen for photosensitization making them effective where hypoxia has taken hold.

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Cis‐TransPhotoisomerization of Stilbenes and Stilbene‐Like Molecules

Cited by 57 publications

References 546 publications

Anticancer phototherapy using activation of E -combretastatins by two-photon–induced isomerization

Anticancer phototherapy using activation of E -combretastatins by two-photon–induced isomerization

Fluorescence lifetime imaging of E-combretastatin uptake and distribution in live mammalian cells

New Approaches to Photodynamic Therapy from Types I, II and III to Type IV Using One or More Photons

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