Search

Clinically approved photodynamic therapy (PDT) is a minimally invasive treatment procedure that uses three key components: photosensitization, a light source, and tissue oxygen. However, the photodynamic effect is limited by both the photophysical properties of photosensitizers as well as their low selectivity, leading to damage to adjacent normal tissue and/or inadequate biodistribution. Nanoparticles (NPs) represent a new option for PDT that can overcome most of the limitations of conventional photosensitizers and can also promote photosensitizer accumulation in target cells through enhanced permeation and retention effects. In this in vitro study, the photodynamic effect of TPP photosensitizers embedded in polystyrene nanoparticles was observed on the non-tumor NIH3T3 cell line and HeLa and G361 tumor cell lines. The efficacy was evaluated by viability assay, while reactive oxygen species production, changes in membrane mitochondrial potential, and morphological changes before and after treatment were imaged by atomic force microscopy. The tested nanoparticles with embedded TPP were found to become cytotoxic only after activation by blue light (414 nm) due to the production of reactive oxygen species. The photodynamic effect observed in this evaluation was significantly higher in both tumor lines than the effect observed in the non-tumor line, and the resulting phototoxicity depended on the concentration of photosensitizer and irradiation time. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of N -aryl-2,6-diphenyl-2 H -pyrazolo[4,3- c ]pyridin-7-amines. • Photodynamic effect and no dark toxicity in melanoma G361 cells. • Cell death through production of ROS and DNA damage. A small series of N -aryl-2,6-diphenyl-2 H -pyrazolo[4,3- c ]pyridin-7-amines was synthesized from easily accessible 1-phenyl-1 H -pyrazol-3-ol via 7-iodo-2,6-diphenyl-2 H -pyrazolo[4,3- c ]pyridine and 7-iodo-4-methyl-2,6-diphenyl-2 H -pyrazolo[4,3- c ]pyridine intermediates and their subsequent use in palladium catalyzed Buchwald-Hartwig cross-coupling reaction with various anilines. Majority of the compounds were not significantly cytotoxic to melanoma G361 cells in the dark up to 10 µM concentration, but their activity could be increased by irradiation with visible blue light (414 nm). The most active compound 10 possessed EC 50 values of 3.5, 1.6 and 0.9 µM in cells irradiated with 1, 5 and 10 J/cm2, respectively. The treatment caused generation of reactive oxygen species in cells and extensive DNA damage, documented by the comet assay and by detection of phosphorylated histone H2A.X, followed by apoptotic cell death. Our results suggest that N -aryl-2,6-diphenyl-2 H -pyrazolo[4,3- c ]pyridin-7-amines could serve as a potential source of photosensitizing compounds with anticancer activities. [ABSTRACT FROM AUTHOR]