Effect of Photosensitizers Photosens, Photodithazine and Hypericin on Glioma Сells and Primary Neuronal Cultures: a Comparative Analysis

Abstract

The aim of the study was to compare the effect of photosensitizers photosens, photodithazine, and hypericin on primary brain cell cultures, and assess their toxic effect on tumor and normal nervous cells in order to choose the optimal photodynamic agent for glioma therapy.Materials and Methods. The cytotoxicity of photosens (NIOPIK, Russia), photodithazine (Veta-grand, Russia) and hypericin (Merck KGaA; Sigma-Aldrich, Germany) was assessed on primary brain cell cultures obtained from C57BL/6 mice (gestation day 18). On day 14 of cultivation, the tested photosensitizers were added to a culture medium at concentrations of 0.1, 1, 10, 50, and 100 µM. Then the cultures were placed in a СО 2 -incubator in the dark. The viability of primary neuronal cultures was estimated on days 3 and 7 after photosensitizer application. Using confocal microscopy, we analyzed the rate of entry and subcellular localization of the tested agents in the primary neuronal cells. Statistical analysis was performed in SigmaPlot 11.0 (Systat Software Inc., USA) using ANOVA.Results. We analyzed the absorption and fluorescence spectra of the tested photosensitizers. Photosens and photodithazine showed the presence of absorption maximum in short-and long-wave spectral ranges. Hypericin was characterized by a complex spectrum with many peaks in both blue-violet and orange-red spectral ranges. Cell viability analysis revealed that high concentrations of photosensitizers caused a pronounced toxic effect on nervous cells. The most marked effect was shown for photodithazine. Photosens exhibited the lowest accumulation rate in primary neuronal cells. Photosens and hypericin were found to have a high phototoxic effect on glioma, and demonstrated low dark toxicity for normal brain cells.Conclusion. The photosensitizers hypericin and photosens are the least toxic for nervous tissue, though effectively penetrating in tumor cells. These properties enable to consider them as prospective photodynamic agents for clinic.

Photobleaching of non-covalent complexes of folic acid and photosensitizers

“…Anionic Photosens is a mixture of di-, tri-, and tetra-substituted fractions of sulfonated aluminum phthalocyanine with the number of sulfo group 3,4 [13]. The complexes of Photosens and FA were obtained with the molar ratio of components FA/Photosens = 5.8.…”

Surufatinib combined with photodynamic therapy induces ferroptosis to inhibit cholangiocarcinoma in vitro and in tumor models

“…Therefore, the efficacy of PDT can be enhanced by enhancing ferroptosis. Some studies have summarized the synergistic mechanism and application fields of PDT and ferroptosis in recent years (Mishchenko et al, 2021;Huang et al, 2023). PDT can produce ROS and H 2 O 2 through type I photochemical reactions and the H 2 O 2 can further induce ferroptosis by promoting the Fenton reaction.…”

Activated aggregation‐induced emission therapeutics agents for triggering regulated cell death

“…[ 35,36 ] Concurrently, the evolving comprehension of cell death processes has highlighted an alternative strategy for instigating tumor cell demise through non‐apoptotic RCD pathways. [ 37,38 ] These include autophagy, [ 39,40 ] pyroptosis, [ 41,42 ] necroptosis, [ 43–45 ] immunogenic cell death (ICD), [ 46–48 ] ferroptosis, [ 49,50 ] and the recently unearthed cuproptosis. [ 51,52 ] A mounting body of evidence attests to the capacity of phototherapy and SDT to not only precipitate the apoptosis of tumor cells but also to instigate non‐apoptotic RCD (Figure 1).…”