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.

Reactive oxygen species generation in aqueous solutions containing GdVO4:Eu3+ nanoparticles and their complexes with methylene blue.

It this letter, we report the study of free radicals and reactive oxygen species (ROS) generation in water solutions containing gadolinium orthovanadate GdVO4:Eu3+ nanoparticles (VNPs) and their complexes with methylene blue (MB) photosensitizer. The catalytic activity was studied under UV-Vis and X-ray irradiation by three methods (conjugated dienes test, OH· radical, and singlet oxygen detection). It has been shown that the VNPs-MB complexes reveal high efficiency of ROS generation under UV-Vis irradiation associated with both high efficiency of OH· radicals generation by VNPs and singlet oxygen generation by MB due to nonradiative excitation energy transfer from VNPs to MB molecules. Contrary to that under X-ray irradiation, the strong OH . radicals scavenging by VNPs has been observed.

Oscillations of Cerium Oxidation State Driven by Oxygen Diffusion in Colloidal Nanoceria (CeO2 - x ).

The redox performance of CeO2 - x nanocrystals (nanoceria) is always accompanied by the switching of cerium oxidation state between Ce3+ and Ce4+. We monitored Ce3+ â†’ Ce4+ oxidation of nanoceria stimulated by oxidant in aqueous colloidal solutions controlling the luminescence of Ce3+ ions located at different distances from nanoceria surface. The observed Ce3+ luminescence changes indicate that Ce3+ â†’ Ce4+ reaction develops inside nanoceria being triggered by the diffusing oxygen originated from the water splitting on oxidized nanoceria surface. We present the first observation of the pronounced oscillations of Ce3+ luminescence intensity arising from Ce3+ â†” Ce4+ reversible switching. This threshold effect is to be driven by uptaking and releasing oxygen by nanoceria, when the concentration of oxygen vacancies in nanoceria lattice, oxidant concentration in colloidal solution, and temperature reach certain critical values. So, the ability of nanoceria to uptake and release oxygen depending on the environmental redox conditions really makes it the self-sufficient eternal antioxidant.

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.

Size and shape influence of luminescent orthovanadate nanoparticles on their accumulation in nuclear compartments of rat hepatocytes.

In this paper the process of nonfunctionalized negatively charged orthovanadate nanoparticle accumulation and redistribution in cells dependent on their shape and size was investigated. Aqueous colloidal solutions of nReVO4:Eu(3+) (Re=Gd, Y, La) luminescent nanocrystals of different sizes and shapes have been synthesized. The average sizes of spherical particles were 2, 20, and 300 nm, of spindle-like particles - 22×6.3 nm, and of rod-like particles - 57×4.4 nm. Luminescence of nReVO4:Eu(3+) nanocrystals was effectively excited by UV and visible irradiation. By means of luminescence microscopy and luminescence microspectroscopy, it has been revealed that spherical nanocrystals with an average diameter of 2 nm tend to accumulate mainly in the rat hepatocyte nuclei in situ and also in the isolated nuclei of these cells. An additional experiment has shown that nanoparticles reveal tropism to nuclear structural components. The penetration into nuclei does not require any modifications of the surface of nanoparticle and is governed by the shape and size of nanoparticle and also is determined by the cellular type.

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.