Mechanisms of Phototoxic Effects of Cationic Porphyrins on Human Cells In Vitro

Abstract

The toxic effects of four cationic porphyrins on various human cells were studied in vitro. It was found that, under dark conditions, porphyrins are almost nontoxic, while, under the action of light, the toxic effect was observed starting from nanomolar concentrations. At a concentration of 100 nM, porphyrins caused inhibition of metabolism in the MTT test in normal and cancer cells. Furthermore, low concentrations of porphyrins inhibited colony formation. The toxic effect was nonlinear; with increasing concentrations of various porphyrins, up to about 1 μM, the effect reached a plateau. In addition to the MTT test, this was repeated in experiments examining cell permeability to trypan blue, as well as survival after 24 h. The first visible manifestation of the toxic action of porphyrins is blebbing and swelling of cells. Against the background of this process, permeability to porphyrins and trypan blue appears. Subsequently, most cells (even mitotic cells) freeze in this swollen state for a long time (24 and even 48 h), remaining attached. Cellular morphology is mostly preserved. Thus, it is clear that the cells undergo mainly necrotic death. The hypothesis proposed is that the concentration dependence of membrane damage indicates a limited number of porphyrin targets on the membrane. These targets may be any ion channels, which should be considered in photodynamic therapy.

Antimicrobial Potency of Fmoc-Phe-Phe Dipeptide Hydrogels with Encapsulated Porphyrin Chromophores Is a Promising Alternative in Antimicrobial Resistance

“…Importantly, the prepared hydrogels did not show any cytotoxic effect on the NIH3T3 fibroblasts without light irradiation. This observation aligns with the findings reported in the literature, namely that in the absence of light, cationic porphyrins exhibit negligible cytotoxicity on various human cell lines [51]. Both cytocompatibility and degradability are critical characteristics of hydrogels that determine the efficacy of topical applications, for example, in wound healing [52].…”

The Potential of Narrow-Band Imaging as a Novel Light Source for Photodynamic Therapy for Superficial Cancers via Endoscopes

“…Studies suggest that irradiation with blue light inhibits tumor growth in various cancer cell lines through diverse mechanisms [ 27 - 34 ]. In the context of photoreceptors, Ohara et al reported that blue light (λ = 470 nm, irradiance 5.7 mW/cm 2 ) inhibited the growth of B16 melanoma cells [ 27 ].…”

“…Zarska et al also evaluated the photodynamic effect of α, β, γ, δ-tetrakis (1-methylpyridinium-4-yl) porphyrin p-toluenesulfonate (TMPyP) and zinc-4-sulfonatophenyl porphyrin (ZnTPPS4) on the HeLa (cervical cancer) and G361 (human skin malignant melanoma) cell lines with blue light (λ = 414 nm) irradiation [ 32 ]. Yegorov et al recently reported the toxicity of blue light with porphyrins (cationic porphyrin P4 (TMPyP4) and its amphiphilic derivative porphyrin P1 containing carboxyl groups, as well as their zinc-containing analogues ZnP4 and ZnP1) in normal (human mesenchymal stromal cells KO-16, an immortalized human embryonic fibroblast line (977-hTERT)) and cancer cells (A549 and SK-N-SH) [ 34 ]. They demonstrated that in the presence of blue light for 30 min of irradiation, there was a significant decrease in the viability of all cell lines (concentrations 50 nM).…”

Electrophoretically Co-Deposited Collagen–Lactoferrin Membranes with Enhanced Pro-Regenerative Properties for Oral Soft Tissue Regeneration

“…To evaluate the biocompatibility of Col and Col-LF membranes in vitro, they were tested with two cell lines: keratinocytes (HaCaT line) and fibroblasts (977hTERT embryonic fibroblasts [52]). Cells were cultured using growth medium of the following composition: DMEM/F12 (1:1, BioloT, Saint Petersburg, Russia), gentamicin (50 µg/mL, PanEco, Moscow, Russia), and fetal calf serum FBS (10%, ThermoFisher, Waltham, MA, USA).…”