Magnetic nanoparticles Fe₃O₄ doped by different amounts of Y³⁺ (0, 0.1, 1, 10 %) ions were designed to obtain maximum heating efficiency in magnetic hyperthermia for cancer treatment. Single phase formation was evident by XRD measurements. Improved magnetization value was obtained for the Fe₃O₄ sample with 1% of Y³⁺ doping. The specific absorption rate (SAR) and intrinsic loss of power (ILP) values for prepared colloids was obtained in water. The best results was estimated for Fe₃O₄ with 0.1% of Y³⁺ ions (SAR=194 W/g and ILP=1.85 nHm²/kg for magnetic field of 16kA/m with the frequency 413 kHz). The excellent biocompatibility with low cell cytotoxicity of Fe₃O₄:Y nanoparticles was observed. Immediately after magnetic hyperthermia treatment with Fe₃O₄:0.1%Y, the 4T1 cells viability decrease was observed (77% for 35 μg/ml, 68 % for 100 μg/ml). These results suggest that Fe₃O₄ doped by Y³⁺ ions nanoparticles are suitable for biomedical applications, especially for the hyperthermia treatment.

Multicolor upconversion of SiO₂-coated nanoparticles using for cells imaging and reactive oxygen species generation.

Nanostructures as color-tunable luminescent markers have become major, promising tools for bioimaging and biosensing. In this paper separated molybdate/Gd ₂ O ₃ doped rare earth ions (erbium, Er ³⁺ and ytterbium, Yb ³⁺ ) core–shell nanoparticles (NPs), were fabricated by a one-step homogeneous precipitation process. Emission properties were studied by cathodo- and photoluminescence. Scanning electron and transmission electron microscopes were used to visualize and determine the size and shape of the NPs. Spherical NPs were obtained. Their core–shell structures were confirmed by x-ray diffraction and energy-dispersive x-ray spectroscopy measurements. We postulated that the molybdate rich core is formed due to high segregation coefficient of the Mo ion during the precipitation. The calcination process resulted in crystallization of δ / ξ (core/shell) NP doped Er and Yb ions, where δ —gadolinium molybdates and ξ —molybdates or gadolinium oxide. We confirmed two different upconversion mechanisms. In the presence of molybdenum ions, in the core of the NPs, Yb ³⁺ – MoO 4 2 − (∣ ² F _7/2 , ³ T ₂ 〉) dimers were formed. As a result of a two 980 nm photon absorption by the dimer, we observed enhanced green luminescence in the upconversion process. However, for the shell formed by the Gd ₂ O ₃ :Er, Yb NPs (without the Mo ions), the typical energy transfer upconversion takes place, which results in red luminescence. We demonstrated that the NPs were transported into cytosol of the HeLa and astrocytes cells by endocytosis. The core–shell NPs are sensitive sensors for the environment prevailing inside (shorter luminescence decay) and outside (longer luminescence decay) of the tested cells. The toxicity of the NPs was examined using MTT assay.

In recent years, rare-earth-doped upconverting nanoparticles (UCNPs) have been widely used in different life sciences due to their unique properties. Nanoparticles have become a multifunctional and promising new approach to neurobiological disorders and have shown extraordinary application potential to overcome the problems related to conventional treatment strategies. This study evaluated the internalization mechanisms, bio-distribution, and neurotoxicity of NaYF₄:20%Yb³⁺,2%Er³⁺ UCNPs in rat organotypic hippocampal slices. TEM results showed that UCNPs were easily internalized by hippocampal cells and co-localized with selected organelles inside neurons and astrocytes. Moreover, the UCNPs were taken into the neurons via clathrin- and caveolae-mediated endocytosis. Propidium iodide staining and TEM analysis did not confirm the adverse effects of UCNPs on hippocampal slice viability and morphology. Therefore, UCNPs may be a potent tool for bio-imaging and testing new therapeutic strategies for brain diseases in the future.

Water-soluble upconversion nanoparticles (UCNPs), based on polyvinylpyrrolidone (PVP)-coated NaYF₄:Er³⁺,Yb³⁺,Gd³⁺, with various concentrations of Gd³⁺ ions and relatively high upconversion efficiencies, were synthesized. The internalization and cytotoxicity of the thus obtained UCNPs were evaluated in three cell lines (HeLa, HEK293 and astrocytes). No cytotoxicity was observed even at concentrations of UCNPs up to 50 μg ml⁻¹. The fate of the UCNPs within the cells was studied by examining their upconversion emission spectra with confocal microscopy and confirming these observations with transmission electron microscopy. It was found that the cellular uptake of the UCNPs occurred primarily by clathrin-mediated endocytosis, whereas they were secreted from the cells via lysosomal exocytosis. The results of this study, focused on the mechanisms of the cellular uptake, localization and secretion of UCNPs, demonstrate, for the first time, the co-localization of UCNPs within discrete cell organelles.

Tuberous sclerosis complex (TSC) is a rare, multi-system genetic disease with serious neurological and mental symptoms, including autism. Mutations in the TSC1/TSC2 genes lead to the overactivation of mTOR signalling, which is also linked to nonsyndromic autism. Our aim was to analyse synaptic pathology in a transgenic model of TSC: two-month-old male B6;129S4-Tsc2^tm1Djk/J mice with Tsc2 haploinsufficiency. Significant brain-region-dependent alterations in the expression of several synaptic proteins were identified. The most prominent changes were observed in the immunoreactivity of presynaptic VAMP1/2 (ca. 50% increase) and phospho-synapsin-1 (Ser62/67) (ca. 80% increase). Transmission electron microscopy demonstrated serious ultrastructural abnormalities in synapses such as a blurred structure of synaptic density and a significantly increased number of synaptic vesicles. The impairment of synaptic mitochondrial ultrastructure was represented by excessive elongation, swelling, and blurred crista contours. Polyribosomes in the cytoplasm and swollen Golgi apparatus suggest possible impairment of protein metabolism. Moreover, the delamination of myelin and the presence of vacuolar structures in the cell nucleus were observed. We also report that Tsc2^+/− mice displayed increased brain weights and sizes. The behavioural analysis demonstrated the impairment of memory function, as established in the novel object recognition test. To summarise, our data indicate serious synaptic impairment in the brains of male Tsc2^+/− mice.