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Applicability of new degradable hypericin-polymer-conjugates as photosensitizers: principal mode of action demonstrated by in vitro models

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Abstract

Two series of water soluble novel conjugates of the photosensitizer hypericin were prepared and evaluated for their use as agents for photodynamic therapy, with covalently and non-covalently loaded hypericin on functionalised, hydrolytically degradable inorganic-organic hybrid polyphosphazenes. The conjugates showed excellent aqueous solubility and similar fluorescence spectra to pristine hypericin Detailed in vitro investigations revealed that the substances were non-toxic in the dark over a wide concentration range, but displayed phototoxicity upon irradiation. Cell uptake studies showed rapid uptake with localization of hypericin observed in endoplasmic reticulum, Golgi complex and particularly in the lysosomes. Furthermore, a DNA fragmentation assay revealed that the photosensitizer conjugates are efficient inducers of apoptosis with some tumor cell selectivity caused by faster and enhanced accumulation in A431 than in HaCaT cells, and thus a moderately higher phototoxicity of A431 compared to HaCaT cells. These novel photosensitizer conjugates hence represent viable hydrolytically degradable alternatives for the advanced delivery of hypericin.

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Authors and Affiliations

  1. Division of Molecular Tumor Biology, Department of Molecular Biology, University of Salzburg, Hellbrunnerstrasse 34, 5020, Salzburg, Austria

    Daniela Feinweber, Thomas Verwanger & Barbara Krammer

  2. Institute of Polymer Chemistry, Johannes Kepler University Linz, Welser Strasse 42, 4060, Leonding, Austria

    Oliver Brüggemann & Ian Teasdale

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  1. Daniela Feinweber
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  2. Thomas Verwanger
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  3. Oliver Brüggemann
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  4. Ian Teasdale
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  5. Barbara Krammer
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Correspondence to Ian Teasdale or Barbara Krammer.

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Electronic supplementary information (ESI) available. See DOI: 10.1039/c4pp00251b

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Feinweber, D., Verwanger, T., Brüggemann, O. et al. Applicability of new degradable hypericin-polymer-conjugates as photosensitizers: principal mode of action demonstrated by in vitro models. Photochem Photobiol Sci 13, 1607–1620 (2014). https://doi.org/10.1039/c4pp00251b

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