Novel zinc‑ and silicon‑phthalocyanines as photosensitizers for photodynamic therapy of cholangiocarcinoma

Schmidt,Jacob; Kuzyniak,Weronika; Berkholz,Janine; Steinemann,Gustav; Ogbodu,Racheal; Hoffmann,Björn; Nouailles,Geraldine; Gürek,Ayşe Gül; Nitzsche,Bianca; Höpfner,Michael

doi:10.3892/ijmm.2018.3620

Novel zinc‑ and silicon‑phthalocyanines as photosensitizers for photodynamic therapy of cholangiocarcinoma

Authors:
- Jacob Schmidt
- Weronika Kuzyniak
- Janine Berkholz
- Gustav Steinemann
- Racheal Ogbodu
- Björn Hoffmann
- Geraldine Nouailles
- Ayşe Gül Gürek
- Bianca Nitzsche
- Michael Höpfner
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Affiliations: Institute of Physiology, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany, Department of Infectious Diseases and Pulmonary Medicine, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany, Department of Chemistry, Gebze Technical University, Gebze, Kocaeli 41400, Turkey
Published online on: April 16, 2018 https://doi.org/10.3892/ijmm.2018.3620
Pages: 534-546

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Abstract

Photodynamic therapy (PDT) has emerged as an effective and minimally invasive cancer treatment modality. In the present study, two novel phthalocyanines, tetra‑triethyleneoxysulfonyl substituted zinc phthalocyanine (ZnPc) and dihydroxy‑2,9(10),16(17),23(24)‑tetrakis(4,7,10‑trioxaundecan‑1‑sulfonyl) silicon phthalocyanine (Pc32), were investigated as photosensitizers (PS) for PDT of cholangiocarcinoma (CC). ZnPc showed a pronounced dose‑dependent and predominantly cytoplasmic accumulation in EGI‑1 and TFK‑1 CC cell lines. Pc32 also accumulated in the CC cells, but this was less pronounced. Without photoactivation, the PS did not exhibit any antiproliferative or cytotoxic effects. Upon photoactivation, ZnPc induced the formation of reactive oxygen species (ROS) and immediate phototoxicity, leading to a dose‑dependent decrease in cell proliferation, and an induction of mitochondria‑driven apoptosis and cell cycle arrest of EGI‑1 and TFK‑1 cells. Although photoactivated Pc32 also induced ROS formation in the two cell lines, the extent was less marked, compared with that induced by ZnPc‑PDT, and pronounced antipoliferative effects occurred only in the less differentiated EGI‑1 cells, whereas the more differentiated TFK‑1 cells did not show sustained growth inhibition upon Pc32‑PDT induction. In vivo examinations on the antiangiogenic potency of the novel PS were performed using chorioallantoic membrane (CAM) assays, which revealed reduced angiogenic sprouting with a concomitant increase in nonperfused regions and degeneration of the vascular network of the CAM following induction with ZnPc‑PDT only. The study demonstrated the pronounced antiproliferative and antiangiogenic potency of ZnPc as a novel PS for PDT, meriting further elucidation as a promising PS for the photodynamic treatment of CC.

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