Abstract
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.
Highlights
Metal-based phthalocyanines are currently used in industrial applications, but these compounds have properties that make them prospective photosensitizers
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 photodynamic therapy (PDT)
Using this technology we have shown that long time incubation of neuroblastoma cell lines in In-Pc does not significantly hinder cell proliferation when concentration are ≤ 10 μg/ mL
Summary
Metal-based phthalocyanines are currently used in industrial applications, but these compounds have properties that make them prospective photosensitizers. Produce reactive oxygen species upon exposure to light, inducing apoptosis/necrosis pathways and having a long time history in photodynamic therapy (PDT) [1, 2]. PS’s accumulated molecules will be activated upon irradiation with a particular wavelength laser light inducing photochemical and photophysical processes. These processes reside in the energy transfer to the nearby oxygen, transfer that generates reactive oxygen species (mainly singlet oxygen, hydroxyl radical, and superoxide anions). The insertion of heavy metals enhances the inter-system crossing rates This is important because triplet lifetimes are significantly longer than singlet lifetimes, and the triplet-triplet transition has an enhanced absorption compared to corresponding singletsinglet transition [11]
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