Effects of zinc porphyrin and zinc phthalocyanine derivatives in photodynamic anticancer therapy under different partial
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PRECLINICAL STUDIES
Effects of zinc porphyrin and zinc phthalocyanine derivatives in photodynamic anticancer therapy under different partial pressures of oxygen in vitro Martin Pola 1 & Hana Kolarova 1 & Jiri Ruzicka 1 & Aleksey Zholobenko 2 & Martin Modriansky 2 & Jiri Mosinger 3,4 & Robert Bajgar 1,5 Received: 3 July 2020 / Accepted: 18 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Summary Photodynamic therapy (PDT) is gradually becoming an alternative method in the treatment of several diseases. Here, we investigated the role of oxygen in photodynamically treated cervical cancer cells (HeLa). The effect of PDT on HeLa cells was assessed by exposing cultured cells to disulphonated zinc phthalocyanine (ZnPcS2) and tetrasulphonated zinc tetraphenylporphyrin (ZnTPPS4). Fluorescence microscopy revealed their different localizations within the cells. ZnTPPS4 seems to be mostly limited to the cytosol and lysosomes, whereas ZnPcS2 is most likely predominantly attached to membrane structures, including plasmalemma and the mitochondrial membrane. Phototoxicity assays of PDT-treated cells carried out under different partial pressures of oxygen showed dose-dependent responses. Interestingly, ZnPcS2 was also photodynamically effective at a minimal level of oxygen, under a nitrogen atmosphere. On the other hand, hyperbaric oxygenation did not lead to a higher PDT efficiency of either photosensitizer. Although both photosensitizers can induce a significant drop in mitochondrial membrane potential, ZnPcS2 has a markedly higher effect on mitochondrial respiration that was completely blocked after two short light cycles. In conclusion, our observations suggest that PDT can be effective even in hypoxic conditions if a suitable sensitizer is chosen, such as ZnPcS2, which can inhibit mitochondrial respiration. Keywords Photosensitizers . Photodynamic therapy . Hyperbaria
Introduction * Robert Bajgar [email protected] 1
Department of Medical Biophysics, Faculty of Medicine and Dentistry, Palacky University in Olomouc, Hnevotinska 3, 775 15 Olomouc, Czech Republic
2
Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University in Olomouc, Hnevotinska 3, 775 15 Olomouc, Czech Republic
3
Department of Inorganic Chemistry, Faculty of Science, Charles University, Hlavova 2030, 128 43 Prague 2, Czech Republic
4
Institute of Inorganic Chemistry of the Czech Academy of Sciences, v.v.i., Husinec-Rez 1001, 250 68 Rez, Czech Republic
5
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc, Hnevotinska 3, 775 15 Olomouc, Czech Republic
Photodynamic therapy utilizes local or systemic administration of a photosensitive compound (photosensitizer), which is predominantly absorbed and stored in pathological tissues or pathogenic microorganisms. The energy of light is transferred via the photosensitizer to oxygen or other molecules that induce serious changes leading to selective damage of the pathol
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