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Drug-induced Photosensitivity

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41. Photosensitization of A2E triggers telomere dysfunction and accelerates retinal pigment epithelium senescence (PubMed)

that telomere dysfunction plays an important role in A2E-based senescence. We further showed that the senescence induced by A2E photosensitization may affect the microenvironment of the retina by expressing several factors of the secretory phenotype (SASP) including IL1B, IL13RA2, and CXCR4 through the NF-κB pathway. We propose that expression of these factors create a pro-inflammatory environment that drives retina degeneration. Moreover, our findings suggest that protecting telomeres is a valuable (...) Photosensitization of A2E triggers telomere dysfunction and accelerates retinal pigment epithelium senescence Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in elderly people. AMD is classified as early, intermediate, advanced non-neovascular, and advanced neovascular forms depending on the clinical features. However, the exact pathogenesis remains unclear. Retinal pigment epithelium (RPE) cells degeneration is a hallmark of AMD. With aging, lipofuscin

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2018 Cell death & disease

42. Targeting of a Photosensitizer to the Mitochondrion Enhances the Potency of Photodynamic Therapy (PubMed)

that the triphenylphosphine derivative (0323) has better mitochondria-targeting efficacy, SOS production, and mitochondria membrane toxicity than either unmodified verteporfin or its guanidinium derivatives. Consistent with this potency, 0323 also induced the most prominent mitochondria swelling, actin depolymerization, pyknosis, and cytochrome C release. We conclude that triphenylphosphine has a better mitochondria-targeting moiety than guanidinium or bis-guanidinium and those PDT photosensitizers with improved (...) Targeting of a Photosensitizer to the Mitochondrion Enhances the Potency of Photodynamic Therapy Photodynamic therapy (PDT) involves use of a photosensitizer, whose activation with light leads to the production of singlet oxygen (SOS), generation of reactive oxygen species (ROS), and initiation of associated cell toxicity. Because a cell's mitochondria constitute sites where oxygen levels are high, ROS can be readily produced, and apoptosis is commonly initiated. Therefore, an ideal PDT agent

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2018 ACS Omega

43. Spiropyran in nanoassemblies as a photosensitizer for photoswitchable ROS generation in living cells †Electronic supplementary information (ESI) available. See DOI: 10.1039/c8sc01148f (PubMed)

, which involved assembling nucleic acids into functional nanoparticles without introducing additional photosensitizers and imaging agents. We found that spiropyran-containing nanoparticles have photoswitching properties for both fluorescence (with a quantum yield of up to 0.27) and singlet oxygen generation (with a quantum yield of up to 0.22) in aqueous solutions and cells, and demonstrated that spiropyrans in nanoassemblies featuring aggregation-induced enhanced photosensitization and emission (...) Spiropyran in nanoassemblies as a photosensitizer for photoswitchable ROS generation in living cells †Electronic supplementary information (ESI) available. See DOI: 10.1039/c8sc01148f Reversibly controlled generation of singlet oxygen from photosensitizing nanosystems has the benefits of selective cell killing and controllable effect time, but is a challenging option for photodynamic therapies. We report a strategy for integrating photochromic spiropyrans into biocompatible cationic polymers

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2018 Chemical Science

44. Hydrogen Bonding Regulates the Rigidity of Liposome‐Encapsulated Chlorin Photosensitizers (PubMed)

Hydrogen Bonding Regulates the Rigidity of Liposome‐Encapsulated Chlorin Photosensitizers Liposomal formulations facilitate the administration of hydrophobic drugs, avoiding precipitation and aggregation phenomena when injected in polar solvents. The integration of the photosensitizer into the liposome may alter the fluidity of the system and, thus, modify the delivery process of the drug. Such a change has been observed for the liposomal formulation of Temoporfin, which is one of the most (...) potent chlorin photosensitizers employed in photodynamic therapy. Here, all-atom molecular dynamics simulations have been performed to identify the nature of the intermolecular interactions that might be responsible of the different lipids freedom of motion when the drug is introduced in the bilayer. It is found that Temoporfin participates as a hydrogen donor in strong hydrogen-bonding interactions with the polar groups of the phospholipids. The theoretical analysis suggests that the rigidity

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2018 ChemistryOpen

45. A semi-automatic and quantitative method to evaluate behavioral photosensitivity in animals based on the optomotor response (OMR) (PubMed)

A semi-automatic and quantitative method to evaluate behavioral photosensitivity in animals based on the optomotor response (OMR) The optomotor response (OMR) is a locomotor behavior of animals that is induced by moving repetitive visual stimuli. This characteristic helps animals particularly when stabilizing and maintaining position in schools and herds. Here, we developed a simple but sensitive method for quantifying the OMR using medaka (Oryzias latipes) as a model. This method, which simply (...) , and total distance of swimming) that are calculated based on a series of x-y coordinates of the moving fish, supported that conclusion and further indicated that both strains perceive light at even longer wavelengths. This low-cost, quantitative, and semi-automatic method would widen the opportunities to unveil behavioral photosensitivity in animals of interest.This article has an associated First Person interview with the first author of the paper.© 2018. Published by The Company of Biologists Ltd.

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2018 Biology open

46. A Study to Evaluate the Pharmacodynamic Activity of E2730 in Adult Participants With Photosensitive Epilepsy

Phase Photosensitive Epilepsy Drug: Placebo Drug: E2730 Phase 2 Detailed Description: Adult participants with epilepsy will be enrolled in this study. This study will consist of 2 phases: Prerandomization and Randomization Phase. The Prerandomization Phase will consist of a Screening Period (up to 3 weeks), during which each participant's study eligibility will be determined and baseline assessments will be conducted. The Randomization Phase will consist of 3 Treatment Periods with a single dose (...) A Study to Evaluate the Pharmacodynamic Activity of E2730 in Adult Participants With Photosensitive Epilepsy A Study to Evaluate the Pharmacodynamic Activity of E2730 in Adult Participants With Photosensitive Epilepsy - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies

2018 Clinical Trials

47. A Study to Evaluate the Pharmacodynamic Activity of E2082 in Adult Participants With Photosensitive Epilepsy

to placebo. Condition or disease Intervention/treatment Phase Photosensitive Epilepsy Drug: Placebo Drug: E2082 Phase 2 Study Design Go to Layout table for study information Study Type : Interventional (Clinical Trial) Estimated Enrollment : 9 participants Allocation: Randomized Intervention Model: Crossover Assignment Intervention Model Description: The study consists of a crossover design in Treatment Periods 1, 2, and 3, followed by an open-label Treatment Period 4. Masking: Quadruple (Participant (...) Last Update Posted: January 24, 2019 Last Verified: August 2018 Individual Participant Data (IPD) Sharing Statement: Plan to Share IPD: Yes Plan Description: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/. Layout table for additional information Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No Keywords provided by Eisai Inc.: E2082 Epilepsy Photosensitive Anti

2018 Clinical Trials

48. Fast and simple method for screening of single-stranded DNA breaking photosensitizers using graphene oxide (PubMed)

effectively, the degree of ultraviolet light-induced broken DNAs could be analyzed by measuring decreased fluorescence after mixing the DNA with graphene oxide. The decrease of fluorescence was highly correlated with the ultraviolet light-irradiating time and concentration of the added drugs. As a result, it was possible to evaluate the efficacy of different ssDNA-breaking photosensitizers in a high-throughput manner. However, conventional methods for the damaged-DNA analysis are time-consuming (...) Fast and simple method for screening of single-stranded DNA breaking photosensitizers using graphene oxide A fast and simple method for screening of ssDNA-breaking photosensitizers was developed using graphene oxide. The ultraviolet light-induced DNA breaks are one of the most harmful DNA damages and cause skin cancer if they are left unrepaired. Since graphene oxide showed relatively strong affinity to the broken DNA than intact DNA, and it quenched fluorescence of the DNA labeling dye

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2018 Nano Convergence

49. Evaluating Nanoshells and a Potent Biladiene Photosensitizer for Dual Photothermal and Photodynamic Therapy of Triple Negative Breast Cancer Cells (PubMed)

in response to laser light that induces cancer cell death. In PDT, photosensitizers introduced to the diseased tissue transfer the absorbed light energy to nearby ground state molecular oxygen to produce singlet oxygen, which is a potent reactive oxygen species (ROS) that is toxic to cancer cells. Although PTT and PDT have been extensively evaluated as independent therapeutic strategies, they each face limitations that hinder their overall success. To overcome these limitations, we evaluated a dual PTT (...) /PDT strategy for treatment of triple negative breast cancer (TNBC) cells mediated by a powerful combination of silica core/gold shell nanoshells (NSs) and palladium 10,10-dimethyl-5,15-bis(pentafluorophenyl)biladiene-based (Pd[DMBil1]-PEG750) photosensitizers (PSs), which enable PTT and PDT, respectively. We found that dual therapy works synergistically to induce more cell death than either therapy alone. Further, we determined that low doses of light can be applied in this approach to primarily

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2018 Nanomaterials

50. Biosynthesis of organic photosensitizer Zn-porphyrin by diphtheria toxin repressor (DtxR)-mediated global upregulation of engineered heme biosynthesis pathway in Corynebacterium glutamicum (PubMed)

Biosynthesis of organic photosensitizer Zn-porphyrin by diphtheria toxin repressor (DtxR)-mediated global upregulation of engineered heme biosynthesis pathway in Corynebacterium glutamicum Zn-porphyrin is a promising organic photosensitizer in various fields including solar cells, interface and biomedical research, but the biosynthesis study has been limited, probably due to the difficulty of understanding complex biosynthesis pathways. In this study, we developed a Corynebacterium glutamicum (...) platform strain for the biosynthesis of Zn-coproporphyrin III (Zn-CP III), in which the heme biosynthesis pathway was efficiently upregulated. The pathway was activated and reinforced by strong promoter-induced expression of hemAM (encoding mutated glutamyl-tRNA reductase) and hemL (encoding glutamate-1-semialdehyde aminotransferase) genes. This engineered strain produced 33.54 ± 3.44 mg/l of Zn-CP III, while the control strain produced none. For efficient global regulation of the complex pathway

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2018 Scientific reports

51. Evaluation of Eosin-Methylene Blue as a Photosensitizer for Larval Control of Aedes aegypti by a Photodynamic Process (PubMed)

Evaluation of Eosin-Methylene Blue as a Photosensitizer for Larval Control of Aedes aegypti by a Photodynamic Process Aedes aegypti (Ae. aegypti) is a competent vector for transmitting important viral diseases such as yellow fever, dengue, chikungunya, and Zika. Several strategies have been applied to avoid Ae. aegypti proliferation by using environmental management, biological, and chemical approaches. However, the development of new methods for effective control of the insect vector (...) population is still needed. Photodynamic control is an alternative way to control the vector population by using a physical approach based on the larval phototoxicity of a photosensitizer. In this context, the present study evaluated the use of eosin-methylene blue (EMB) as a new photosensitizer for photodynamic control of Ae. aegypti larval populations. The photodynamic assays were performed submitting Ae. aegypti third-instar larvae to different EMB concentrations (0.0, 0.5, 1.0, 5.0, 10.0, 50.0

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2018 Insects

52. An optogenetic toolbox of LOV-based photosensitizers for light-driven killing of bacteria (PubMed)

An optogenetic toolbox of LOV-based photosensitizers for light-driven killing of bacteria Flavin-binding fluorescent proteins (FPs) are genetically encoded in vivo reporters, which are derived from microbial and plant LOV photoreceptors. In this study, we comparatively analyzed ROS formation and light-driven antimicrobial efficacy of eleven LOV-based FPs. In particular, we determined singlet oxygen (1O2) quantum yields and superoxide photosensitization activities via spectroscopic assays (...) and performed cell toxicity experiments in E. coli. Besides miniSOG and SOPP, which have been engineered to generate 1O2, all of the other tested flavoproteins were able to produce singlet oxygen and/or hydrogen peroxide but exhibited remarkable differences in ROS selectivity and yield. Accordingly, most LOV-FPs are potent photosensitizers, which can be used for light-controlled killing of bacteria. Furthermore, the two variants Pp2FbFP and DsFbFP M49I, exhibiting preferential photosensitization of singlet

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2018 Scientific reports

53. Photosensitivity and type I IFN responses in cutaneous lupus are driven by epidermal-derived interferon kappa. (PubMed)

baseline type I IFN responses in healthy skin. Increased levels of IFN-κ, such as seen in SLE, amplify and accelerate responsiveness of epithelia to IFN-α and increase keratinocyte sensitivity to UV irradiation. Notably, KO of IFN-κ or inhibition of IFN signalling with baricitinib abrogates UVB-induced apoptosis.Collectively, our data identify IFN-κ as a critical IFN in CLE pathology via promotion of enhanced IFN responses and photosensitivity. IFN-κ is a potential novel target for UVB prophylaxis (...) Photosensitivity and type I IFN responses in cutaneous lupus are driven by epidermal-derived interferon kappa. Skin inflammation and photosensitivity are common in patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE), yet little is known about the mechanisms that regulate these traits. Here we investigate the role of interferon kappa (IFN-κ) in regulation of type I interferon (IFN) and photosensitive responses and examine its dysregulation in lupus skin.mRNA

2018 Annals of the Rheumatic Diseases

54. Development of Novel Photosensitizer Using the <i>Buddleja officinalis</i> Extract for Head and Neck Cancer. (PubMed)

, used in the treatment of inflammation and vascular diseases, shows fluorescence when activated by LED light, and, based on this, we aimed to develop a new photosensitive agent suitable for PDT. MTT, Diff-Quick® staining, and DCF-DA were performed to measure the effects of treating head and neck cancer cells with BO extract and 625 nm LED light (BO-PDT). Cell cycle, TUNEL, and western blot assays, as well as acridine orange staining, were performed to explore the mechanism of BO-PDT-induced cell (...) of proapoptotic protein Bax and a decrease in the expression of the antiapoptotic protein Bcl-2. Moreover, BO-PDT has been shown to induce the autophagy pathway 4 h after treatment, while apoptosis was induced 16 h after treatment. Finally, we confirmed that BO-PDT caused cell death of head and neck cancer cells via the intrinsic pathway. Therefore, we suggest that BO extract can be used as a new photosensitizer in PDT of head and neck cancer.

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2018 Evidence-based Complementary and Alternative Medicine (eCAM)

55. Synchronous delivery of oxygen and photosensitizer for alleviation of hypoxia tumor microenvironment and dramatically enhanced photodynamic therapy (PubMed)

Synchronous delivery of oxygen and photosensitizer for alleviation of hypoxia tumor microenvironment and dramatically enhanced photodynamic therapy Photosensitizer, proper laser irradiation, and oxygen are essential components for effective photodynamic therapy (PDT) in clinical cancer therapy. However, native hypoxic tumoral microenvironment is a major barrier hindering photodynamic reactions in vivo. Thus, we have prepared biocompatible liposomes by loading complexes of oxygen-carrier (...) (hemoglobin, Hb) and photosensitizer (indocyanine green, ICG) for enhanced PDT against hypoxic tumor. Ideal oxygen donor Hb, which is an oxygen-carried protein in red blood cells, makes such liposome which provide stable oxygen supply. ICG, as a photosensitizer, could transfer energy from lasers to oxygen to generate cytotoxic reactive oxygen species (ROS) for treatment. The liposomes loading ICG and Hb (LIH) exhibited efficient tumor homing upon intravenous injection. As revealed by T2-weighted magnetic

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2018 Drug delivery

56. Sulfonamidation of Aryl and Heteroaryl Halides through Photosensitized Nickel Catalysis (PubMed)

Sulfonamidation of Aryl and Heteroaryl Halides through Photosensitized Nickel Catalysis Herein we report a highly efficient method for nickel-catalyzed C-N bond formation between sulfonamides and aryl electrophiles. This technology provides generic access to a broad range of N-aryl and N-heteroaryl sulfonamide motifs, which are widely represented in drug discovery. Initial mechanistic studies suggest an energy-transfer mechanism wherein C-N bond reductive elimination occurs from a triplet

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2018 Angewandte Chemie (International ed. in English)

57. PorphyrinHDL: A Novel Photosensitizing Nanoparticle for Lung Cancer Therapy. (PubMed)

PorphyrinHDL: A Novel Photosensitizing Nanoparticle for Lung Cancer Therapy. We have developed ultrasmall porphyrin-high-density lipoprotein (HDL) nanoparticles (<20 nm), called "porphyrinHDL," that have a high density of porphyrin molecules and dissociate rapidly upon tumor cell accumulation to become fluorescent and photoactive. This is introduced as a novel activatable photosensitizer for image-guided photodynamic therapy (PDT). Here, we report the studies of these nanoparticles targeted (...) . Moreover, porphyrinHDL-PDT significantly induced cell apoptosis in lung tumors (73.2%) without toxicity in normal tissues or damage to adjacent critical structures.SR-BI-targeted porphyrinHDL-mediated PDT of lung cancer is selective and effective in vitro and in vivo. These initial proof-of-principle studies suggest the potential of a "smart" PDT approach for highly selective tumor ablation.Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

2018 Annals of Thoracic Surgery

58. Return of function after CNS axon regeneration: Lessons from injury-responsive intrinsically photosensitive and alpha retinal ganglion cells. (PubMed)

Return of function after CNS axon regeneration: Lessons from injury-responsive intrinsically photosensitive and alpha retinal ganglion cells. This review addresses issues relating to the survival and axon regeneration of both intrinsically photosensitive retinal ganglion cells (ipRGC) and αRGC, and possible ensuing patterns of functional recovery after optic nerve crush, all of which are broadly relevant to recovery from injury in the central nervous system (CNS) as whole. Although much needs (...) to be clarified about the connectivity, function and patterns of myelination of regenerated CNS axons, the results of recent research on activity-induced αRGC axon regeneration associated with functional restitution have highlighted key focal obstacles to recovery including neurotrophic support, axon misguidance, target recognition failure and dysmyelination. Pan RGC survival/axon regeneration requires receptor binding and downstream signalling by a cocktail of growth factors, more generally defined

2018 Progress in Retinal and Eye Research

59. Assessment of Rod, Cone, and Intrinsically Photosensitive Retinal Ganglion Cell Contributions to the Canine Chromatic Pupillary Response. (PubMed)

Assessment of Rod, Cone, and Intrinsically Photosensitive Retinal Ganglion Cell Contributions to the Canine Chromatic Pupillary Response. The purpose of this study was to evaluate a chromatic pupillometry protocol for specific functional assessment of rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) in dogs.Chromatic pupillometry was tested and compared in 37 dogs in different stages of primary loss of rod, cone, and combined rod/cone and optic nerve function (...) , and in 5 wild-type (WT) dogs. Eyes were stimulated with 1-s flashes of dim (1 cd/m2) and bright (400 cd/m2) blue light (for scotopic conditions) or bright red (400 cd/m2) light with 25-cd/m2 blue background (for photopic conditions). Canine retinal melanopsin/Opn4 was cloned, and its expression was evaluated using real-time quantitative reverse transcription-PCR and immunohistochemistry.Mean ± SD percentage of pupil constriction amplitudes induced by scotopic dim blue (scDB), scotopic bright blue (scBB

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2017 Investigative Ophthalmology & Visual Science

60. Photosensitive lichenoid skin reaction to capecitabine. (PubMed)

conservatively without major alteration in treatment.Seventy-three year old female with a diagnosis of stage IV breast cancer undergoing management with capecitabine presents with a rash during the summer months that is biopsy proven to be lichenoid photosensitive rash with likely offending agent being capecitabine. Her treatment was initially held despite having response to treatment, started on topical steroids after evaluation by dermatology. Given her response to treatment, drug was resumed (...) Photosensitive lichenoid skin reaction to capecitabine. Capecitabine is an oral prodrug of fluorouracil, which is a common agent used in the management of many solid tumor malignancies. Dermatologic reaction is common with various chemotherapy agents but is not commonly reported in the use of capecitabine. When adverse reactions of rashes occur, the offending agent is typically removed. We report here an unusual case of photosensitive lichenoid rash due to capecitabine which is managed

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2017 BMC Cancer

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