Effect of novel porphyrazine photosensitizers on normal and tumor brain cells

Abstract

Photodynamic therapy (PDT) is a clinically approved procedure for targeting tumor cells. Though several different photosensitizers have been developed, there is still much demand for novel photosensitizers with improved properties. In this study we aim to characterize the accumulation, localization and dark cytotoxicity of the novel photosensitizers developed in‐house derivatives of porphyrazines (pz I‐IV) in primary murine neuronal cells, as well as to identify the concentrations at which pz still effectively induces death in glioma cells yet is nontoxic to nontransformed cells. The study shows that incubation of primary neuronal and glioma cells with pz I‐IV leads to their accumulation in both types of cells, but their rates of internalization, subcellular localization and dark toxicity differ significantly. Pz II was the most promising photosensitizer. It efficiently killed glioma cells while remaining nontoxic to primary neuronal cells. This opens up the possibility of evaluating pz II for experimental PDT for glioma.

Targeting immunogenic cancer cell death by photodynamic therapy: past, present and future

“…This can be detrimental for several cell types, and particularly brain cells, as morphofunctional disorders in neuron-glial networks may lead to significant disruption of central nervous functions and aggravate the patient’s condition. 53 54 …”

Cyanoarylporphyrazines with High Viscosity Sensitivity: A Step towards Dosimetry-Assisted Photodynamic Cancer Treatment

“…This is in accordance with the amphiphilic properties of the compounds. Of note, we previously reported that in murine neurons, both dyes were mostly held in vesicles with partial localization of pz II in ER [ 25 ]. Thus, the origin and properties of the cancer cells can influence the intracellular distribution of pz .…”

“…The idea to use cyanoarylporphyrazines to follow viscosity changes during PDT was firstly presented for fluorophenyl derivative [ 20 ]. In the present work, we described two porphyrazines with several benefits over previously published compounds: a red shift of absorption and emission maxima that is important for future in vivo application; higher PDT activity against cancer cells and large photodynamic index; and low toxicity against neuronal cells [ 25 ], which allows pz IV and especially pz II application for treatment of gliomas. We assume that real-time assessment of fluorescence lifetime of pz II and pz IV provides a possibility for light dosimetry and correction of the irradiation regimen.…”

“…Maintaining a low toxicity effect for normal tissues in the organism is one of the essential requirements for photosensitizers. Our previous in vitro studies showed that pz II and pz IV had a light and mild cytotoxic effect, respectively, for primary neuronal cultures, which are among the most sensitive cells to any physicochemical stimuli and stress [ 25 ], which shows good promise for the future in vivo application of both of these compounds. In the present study, we have shown lower photoinduced toxicity of pz II and pz IV against normal keratinocytes compared to skin cancer cells.…”

“…Moreover, in our previous study, we showed that several compounds of pz group ( pz I–IV ) can be considered as candidate photosensitizers for PDT treatment of glioma [ 25 ]. Of note, the special requirement for brain tumors is the minimal impact of photosensitizers on neurons functioning.…”