Novel zinc phthalocyanine as a promising photosensitizer for photodynamic treatment of esophageal cancer

  • Authors:
    • Weronika Kuzyniak
    • Jacob Schmidt
    • Wojciech Glac
    • Janine Berkholz
    • Gustav Steinemann
    • Björn Hoffmann
    • Eugeny A. Ermilov
    • Ayşe Gül Gürek
    • Vefa Ahsen
    • Bianca Nitzsche
    • Michael Höpfner
  • View Affiliations

  • Published online on: January 17, 2017     https://doi.org/10.3892/ijo.2017.3854
  • Pages: 953-963
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Abstract

Photodynamic therapy (PDT) has gathered much attention in the field of cancer treatment and is increasingly used as an alternative solution for esophageal cancer therapy. However, there is a constant need for improving the effectiveness and tolerability of the applied photosensitizers (PS). Here, we propose tetra-triethyleneoxysulfonyl substituted zinc phthalocyanine (ZnPc) as a promising PS for photodynamic treatment of esophageal cancer. ZnPc-induced phototoxicity was studied in two human esophageal cancer cell lines: OE-33 (adenocarcinoma) and Kyse-140 (squamous cell carcinoma). In vitro studies focused on the uptake and intracellular distribution of the novel ZnPc as well as on its growth inhibitory potential, reactive oxygen species (ROS) formation and the induction of apoptosis. The chicken chorioallantoic membrane assay (CAM assay) and studies on native Wistar rats were employed to determine the antineoplastic and antiangiogenic activity of ZnPc-PDT as well as the tolerability and safety of non-photoactivated ZnPc in vivo. ZnPc was taken up by cancer cells in a dose- and time-dependent manner and showed a homogeneous cytoplasmic distribution. Photoactivation of ZnPc-loaded (1-10 µM) cells led to a dose-dependent growth inhibition of esophageal adenocarcinoma and squamous cell carcinoma cells of >90%. The antiproliferative effect was based on ROS-induced cytotoxicity and the induction of mitochondria-driven apoptosis. In vivo studies on esophageal tumor plaques grown on the CAM revealed pronounced antiangiogenic and antineoplastic effects. ZnPc-PDT caused long-lasting changes in the vascular architecture and a marked reduction of tumor feeding blood vessels. Animal studies confirmed the good tolerability and systemic safety of ZnPc, as no changes in immunological, behavioral and organic parameters could be detected upon treatment with the non-photoactivated ZnPc. Our findings show the extraordinary photoactive potential of the novel ZnPc as a photosensitizer for PDT of esophageal cancer.
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March-2017
Volume 50 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kuzyniak W, Schmidt J, Glac W, Berkholz J, Steinemann G, Hoffmann B, Ermilov EA, Gürek AG, Ahsen V, Nitzsche B, Nitzsche B, et al: Novel zinc phthalocyanine as a promising photosensitizer for photodynamic treatment of esophageal cancer. Int J Oncol 50: 953-963, 2017
APA
Kuzyniak, W., Schmidt, J., Glac, W., Berkholz, J., Steinemann, G., Hoffmann, B. ... Höpfner, M. (2017). Novel zinc phthalocyanine as a promising photosensitizer for photodynamic treatment of esophageal cancer. International Journal of Oncology, 50, 953-963. https://doi.org/10.3892/ijo.2017.3854
MLA
Kuzyniak, W., Schmidt, J., Glac, W., Berkholz, J., Steinemann, G., Hoffmann, B., Ermilov, E. A., Gürek, A. G., Ahsen, V., Nitzsche, B., Höpfner, M."Novel zinc phthalocyanine as a promising photosensitizer for photodynamic treatment of esophageal cancer". International Journal of Oncology 50.3 (2017): 953-963.
Chicago
Kuzyniak, W., Schmidt, J., Glac, W., Berkholz, J., Steinemann, G., Hoffmann, B., Ermilov, E. A., Gürek, A. G., Ahsen, V., Nitzsche, B., Höpfner, M."Novel zinc phthalocyanine as a promising photosensitizer for photodynamic treatment of esophageal cancer". International Journal of Oncology 50, no. 3 (2017): 953-963. https://doi.org/10.3892/ijo.2017.3854