Toxicological and efficacy assessment of post-transition metal (Indium) phthalocyanine for photodynamic therapy in neuroblastoma.
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.
Faculty of Biology, University of Bucharest, Romania.|Immunobiology Laboratory and Alternative Testing Multi-Disciplinary Team, "Victor Babeş" National Institute of Pathology, Bucharest, Romania.
Monica
M
Neagu
Immunobiology Laboratory and Alternative Testing Multi-Disciplinary Team, "Victor Babeş" National Institute of Pathology, Bucharest, Romania.
Carolina
C
Constantin
Dermatology Department, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
Mircea
M
Tampa
Dermatology Department, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
Clara
C
Matei
Immunobiology Laboratory and Alternative Testing Multi-Disciplinary Team, "Victor Babeş" National Institute of Pathology, Bucharest, Romania.
Andreea
A
Lupu
Immunobiology Laboratory and Alternative Testing Multi-Disciplinary Team, "Victor Babeş" National Institute of Pathology, Bucharest, Romania.|Research Center, Colentina Clinical Hospital, Bucharest, Romania.
Emilia
E
Manole
Nanomedicine Research Group, National Institute of R&D for Chemistry and Petrochemistry - ICECHIM, Bucharest, Romania.|Materials Engineering Department, Valahia University of Targovişte, Romania.
Rodica-Mariana
RM
Ion
Section of Occupational Medicine, University of Messina, Messina, Italy.
Concettina
C
Fenga
Department of Toxicology and Forensic Sciences, Faculty of Medicine, University of Crete, Heraklion, Greece.
Aristidis M
AM
Tsatsakis
D045744:Cell Line, Tumor; D006801:Humans; D007204:Indium / Q000009:adverse effects / Q000627:therapeutic use*; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D054833:Isoindoles; D009447:Neuroblastoma / Q000188:drug therapy*; D010778:Photochemotherapy / Q000009:adverse effects; D026082:Singlet Oxygen / Q000378:metabolism
D007211:Indoles; D054833:Isoindoles; D007204:Indium; D026082:Singlet Oxygen; C013647:phthalocyanine
cellular impedance; indium-phthalocyanine; neuroblastoma; photodynamic therapy; toxicology