Cytotoxicity, Retention, and Anti-inflammatory Effects of a CeO2 Nanoparticle-Based Supramolecular Complex in a 3D Liver Cell Culture Model.

Both cerium oxide (CeOx) nanoparticles and mefenamic acid (MFA) are known anti-inflammatory agents with hepatoprotective properties and are therefore prescribed for one of the major diseases in the world, nonalcoholic fatty liver disease (NAFLD). To study the potential cytotoxicity and anti-inflammatory effects as well as drug retention of a potential therapeutic CeOx/MFA supramolecular complex, a well-standardized hepatic (HepG2) spheroid model was used. Results showed that the highest cytotoxicity for the CeOx/MFA supramolecular complex was found at 50 µg/mL, while effective doses of 0.1 and 1 µg/mL yielded a significant decrease of TNF-α and IL-8 secretion. Time-resolved analysis of HepG2 spheroids revealed a spatiotemporal distribution of the supramolecular complex and limited clearance from the internal microtissue over a period of 8 days in cultivation. In summary, our results point at rapid uptake, distribution, and biostability of the supramolecular complex within the HepG2 liver spheroid model as well as a significant anti-inflammatory response at noncytotoxic levels.

Mitochondrial potential (ΔΨm) changes in single rat hepatocytes: the effect of orthovanadate nanoparticles doped with rare-earth elements.

Rare-earth-based nanoparticles (NPs) are widely used as fluorescent probes for imaging in vitro and in vivo. One of the challenges that restrain NPs applications in biomedical research is their effect on subcellular structures. In this paper, the ability of lanthanide NPs to affect the cellular oxidative balance and alter the mitochondrial function was analyzed. Since size and shape mutually affect the cellular internalization and intracellular distribution of NPs, the investigations were performed with NPs of spherical (GdYVO4:Eu(3+), spindle-(GdVO4: Eu(3+) and rod-like (LaVO4: Eu(3+) shapes. Quantitative microfluorimetry with JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine iodide) as a mitochondrial probe was used for monitoring of the mitochondrial transmembrane potential (ΔΨ m) in single living cells. Changes in the ratio of the JC-1 probe fluorescence were used to analyze the NPs effect on ΔΨ(m). The fastest suppressive effect (within 1 hour) was found for spherical NPs. Gradual lowering of ΔΨ(m) was observed at the exposure of cells within 24 hours for all types of NPs. Exogenous thiols were required for ΔΨ(m) protection. The protective role of exogenous glutathione (GSH) proves that the increase of reactive oxygen species (ROS) formation with depletion of GSH can mediate NPs toxicity. The dynamics of the shape-dependent effect can be explained by the features of NPs transportation into cells.

Pseudoisocyanine J-aggregate to optical waveguiding crystallite transition: microscopic and microspectroscopic exploration.

Using fluorescent microscopy and microspectroscopy, optical properties and morphology transformations in individual pseudoisocyanine (PIC) J-aggregates in aqueous electrolyte solutions have been explored. A stringlike structure of J-aggregates with a string diameter much less than 1 microm has been observed. Photodestruction of the strings under short-wavelength excitation has been revealed. Rodlike PIC crystallites, about 1 microm in diameter, have been observed with time. The fluorescence spectrum of rodlike crystallites has been found to differ from that of stringlike J-aggregate and from PIC crystal powder spectra. The crystallites are very stable, and their photodestruction has not been observed under any excitation conditions. It has been found that rodlike crystallites in contrast to stringlike J-aggregates possess optical waveguide properties. The luminescence of crystallites can be observed only at the excitation spot and at butt ends located up to hundreds of micrometers from the excitation spot.