Toxicological and efficacy assessment of post-transition metal (Indium) phthalocyanine for photodynamic therapy in neuroblastoma
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Monica Neagu1,2, Carolina Constantin2, Mircea Tampa3, Clara Matei3, Andreea Lupu2, Emilia Manole2,4, Rodica-Mariana Ion5,6, Concettina Fenga7, Aristidis M. Tsatsakis8
1Faculty of Biology, University of Bucharest, Romania
2Immunobiology Laboratory and Alternative Testing Multi-Disciplinary Team, “Victor Babeş” National Institute of Pathology, Bucharest, Romania
3Dermatology Department, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
4Research Center, Colentina Clinical Hospital, Bucharest, Romania
5Nanomedicine Research Group, National Institute of R&D for Chemistry and Petrochemistry – ICECHIM, Bucharest, Romania
6Materials Engineering Department, Valahia University of Targovişte, Romania
7Section of Occupational Medicine, University of Messina, Messina, Italy
8Department of Toxicology and Forensic Sciences, Faculty of Medicine, University of Crete, Heraklion, Greece
Carolina Constantin, email: [email protected]
Keywords: photodynamic therapy, neuroblastoma, indium-phthalocyanine, toxicology, cellular impedance
Received: March 25, 2016 Accepted: September 02, 2016 Published: September 10, 2016
Metallo-phthalocyanines due to their photophysical characteristics as high yield of triplet state and long lifetimes, appear to be good candidates for photodynamic therapy (PDT). Complexes with diamagnetic metals such as Zn2+, Al3+ Ga3+ and In3+meet such requirements and are recognized as potential PDT agents. Clinically, Photofrin® PDT in neuroblastoma therapy proved in pediatric subjects diagnosed with progressive/recurrent malignant brain tumors increased progression free survival and overall survival outcome. Our study focuses on the dark toxicity testing of a Chloro-Indium-phthalocyanine photosensitizer (In-Pc) upon SH-SY5Y neuroblastoma cell line and its experimental in vitro PDT. Upon testing, In-Pc has shown a relatively high singlet oxygen quantum yield within the cells subjected to PDT (0.553), and 50 μg/mL IC50. Classical toxicological and efficacy assessment were completed with dynamic cellular impedance measurement methodology. Using this technology we have shown that long time incubation of neuroblastoma cell lines in In-Pc (over 5 days) does not significantly hinder cell proliferation when concentration are ≤ 10 μg/mL. When irradiating neuroblastoma cells loaded with non-toxic concentration of In-Pc, 50% of cells entered apoptosis. Transmission electron microscopy has confirmed apoptotic characteristics of cells. Investigating the proliferative capacity of the in vitro treated cells we have shown that cells that “escape” the irradiation protocol, present a reduced proliferative capacity. In conclusion, In-Pc represents another photosensitizer that can display sound PDT properties enhancing neuroblastoma therapy armentarium.
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