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      Properties of halogenated and sulfonated porphyrins relevant for the selection of photosensitizers in anticancer and antimicrobial therapies

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          Abstract

          The impact of substituents on the photochemical and biological properties of tetraphenylporphyrin-based photosensitizers for photodynamic therapy of cancer (PDT) as well as photodynamic inactivation of microorganisms (PDI) was examined. Spectroscopic and physicochemical properties were related with therapeutic efficacy in PDT of cancer and PDI of microbial cells in vitro. Less polar halogenated, sulfonamide porphyrins were most readily taken up by cells compared to hydrophilic and anionic porphyrins. The uptake and PDT of a hydrophilic porphyrin was significantly enhanced with incorporation in polymeric micelles (Pluronic L121). Photodynamic inactivation studies were performed against Gram-positive ( S. aureus, E. faecalis), Gram-negative bacteria ( E. coli, P. aeruginosa, S. marcescens) and fungal yeast ( C. albicans). We observed a 6 logs reduction of S. aureus after irradiation (10 J/cm 2) in the presence of 20 μM of hydrophilic porphyrin, but this was not improved with incorporation in Pluronic L121. A 2–3 logs reduction was obtained for E. coli using similar doses, and a decrease of 3–4 logs was achieved for C. albicans. Rational substitution of tetraphenylporphyrins improves their photodynamic properties and informs on strategies to obtain photosensitizers for efficient PDT and PDI. However, the design of the photosensitizers must be accompanied by the development of tailored drug formulations.

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          Photodynamic therapy (PDT) of cancer: from local to systemic treatment.

          Photodynamic therapy (PDT) requires a medical device, a photosensitizing drug and adequate use of both to trigger biological mechanisms that can rapidly destroy the primary tumour and provide long-lasting protection against metastasis. We present a multidisciplinary view of the issues raised by the development of PDT. We show how spectroscopy, photophysics, photochemistry and pharmacokinetics of photosensitizers determine the mechanism of cell death and clinical protocols. Various examples of combinations with chemotherapies and immunotherapies illustrate the opportunities to potentiate the outcome of PDT. Particular emphasis is given to the mechanisms that can be exploited to establish PDT as a systemic treatment of solid tumours and metastatic disease.
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            Pluronic® block-copolymers in medicine: from chemical and biological versatility to rationalisation and clinical advances

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              Superoxide reacts with hydroethidine but forms a fluorescent product that is distinctly different from ethidium: potential implications in intracellular fluorescence detection of superoxide.

              Hydroethidine (HE) or dihydroethidium (DHE), a redox-sensitive probe, has been widely used to detect intracellular superoxide anion. It is a common assumption that the reaction between superoxide and HE results in the formation of a two-electron oxidized product, ethidium (E+), which binds to DNA and leads to the enhancement of fluorescence (excitation, 500-530 nm; emission, 590-620 nm). However, the mechanism of oxidation of HE by the superoxide anion still remains unclear. In the present study, we show that superoxide generated in several enzymatic or chemical systems (e.g., xanthine/xanthine oxidase, endothelial nitric oxide synthase, or potassium superoxide) oxidizes HE to a fluorescent product (excitation, 480 nm; emission, 567 nm) that is totally different from E+. HPLC measurements revealed that the HE/superoxide reaction product elutes differently from E+. This new product exhibited an increase in fluorescence in the presence of DNA. Mass spectral data indicated that the molecular weight of the HE/superoxide reaction product is 330, while ethidium has a molecular weight of 314. We conclude that the reaction between superoxide and HE forms a fluorescent marker product that is different from ethidium. Potential implications of this finding in intracellular detection and imaging of superoxide are discussed.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: InvestigationRole: VisualizationRole: Writing – original draft
                Role: Data curationRole: Validation
                Role: ConceptualizationRole: MethodologyRole: Resources
                Role: ResourcesRole: Validation
                Role: ResourcesRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                10 October 2017
                2017
                : 12
                : 10
                : e0185984
                Affiliations
                [1 ] Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, Krakow, Poland
                [2 ] Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
                [3 ] Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland
                [4 ] Chemistry Department, University of Coimbra, Coimbra, Portugal
                Massachusetts General Hospital, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-8791-7035
                Article
                PONE-D-17-26529
                10.1371/journal.pone.0185984
                5634595
                29016698
                b4da7aaf-3249-4dbb-9b75-e3eb5835a700
                © 2017 Pucelik et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 14 July 2017
                : 24 September 2017
                Page count
                Figures: 10, Tables: 3, Pages: 22
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100004281, Narodowe Centrum Nauki;
                Award ID: UMO-2016/22/E/NZ7/00420
                Award Recipient :
                This work was funded by National Science Center (NCN), Poland within the Sonata Bis grant no 0085/IP3/2015/73 given to JMD.
                Categories
                Research Article
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Porphyrins
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Porphyrins
                Physical Sciences
                Physics
                Electromagnetic Radiation
                Luminescence
                Fluorescence
                Physical Sciences
                Chemistry
                Chemical Elements
                Oxygen
                Biology and Life Sciences
                Biochemistry
                Oxidative Damage
                Reactive Oxygen Species
                Biology and Life Sciences
                Organisms
                Eukaryota
                Fungi
                Yeast
                Candida
                Candida Albicans
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Fungal Pathogens
                Candida Albicans
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Fungal Pathogens
                Candida Albicans
                Biology and Life Sciences
                Mycology
                Fungal Pathogens
                Candida Albicans
                Research and Analysis Methods
                Experimental Organism Systems
                Yeast and Fungal Models
                Candida Albicans
                Research and Analysis Methods
                Spectrum Analysis Techniques
                Spectrophotometry
                Fluorophotometry
                Fluorescence Spectrometry
                Biology and Life Sciences
                Microbiology
                Bacteriology
                Gram Negative Bacteria
                Physical Sciences
                Physics
                Electromagnetic Radiation
                Luminescence
                Phosphorescence
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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                Uncategorized

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