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“Core/shell” nanocomposites based on magnetic magnetite (Fe3O4) and redox-active cerium dioxide (CeO2) nanoparticles (NPs) are promising in the field of biomedical interests because they can combine the ability of magnetic NPs to heat up in an alternating magnetic field (AMF) with the pronounced antioxidant activity of CeO2NPs. Thus, this report is devoted to Fe3O4/CeO2nanocomposites (NCPs) synthesized by precipitation of the computed amount of “CeO2-shell” on the surface of prefabricated Fe3O4NPs. The X-ray diffraction, X-ray photoelectron spectroscopy, and high-resolution transmission electron microscopy data validated the formation of Fe3O4/CeO2“core/shell”-like NCPs, in which ultrafine CeO2NPs with an average size of approximately 3–3.5 nm neatly surround Fe3O4NPs. The presence of a CeO2“shell” significantly increased the stability of Fe3O4/CeO2NCPs in aqueous suspensions: Fe3O4/CeO2NCPs with “shell thicknesses” of 5 and 7 nm formed highly stable magnetic fluids with ζ-potential values of >+30 mV. The magnetization values of Fe3O4/CeO2NCPs decreased with a growing CeO2“shell” around the magnetic NPs; however, the resulting composites retained the ability to heat efficiently in an AMF. The presence of a CeO2“shell” generates a possibility to precisely regulate tuning of the maximum heating temperature of magnetic NCPs in the 42–50 °C range and stabilize it after a certain time of exposure to an AMF by changing the thickness of the “CeO2-shell”. A great improvement was observed in both antioxidant and antiamyloidogenic activities. It was found that inhibition of insulin amyloid formation, expressed in IC50concentration, using NCPs with a “shell thickness” of 7 nm was approximately 10 times lower compared to that of pure CeO2. For these NCPs, more than 2 times higher superoxide dismutase-like activity was observed. The coupling of both Fe3O4and CeO2results in higher bioactivity than either of them individually, probably due to a synergistic catalytic mechanism.

Monitoring the aggregation of amyloid-prone proteins is critical for understanding the mechanism of amyloid fibril formation. Insulin, when dissolved in low pH buffer, has a surface tension of 61–64 mN m−1, as measured by the pendant drop technique. Formation of insulin amyloid fibrils resulted in the increase of the surface tension values up to 71.2–73.5 mN m−1. The kinetics of fibril formation and fibril morphology were validated by ThT fluorescence and AFM, respectively. The results demonstrate that monitoring the surface tension by the pendant drop technique is a valuable tool for the detection of insulin amyloid aggregation.

Nowadays, determining the disassembly mechanism of amyloids under nanomaterials action is a crucial issue for their successful future use in therapy of neurodegenerative and overall amyloid-related diseases. In this study, the antiamyloid disassembly activity of fullerenes C60and C70dispersed in 1-methyl-2-pyrrolidinone (NMP) toward amyloid fibrils preformed from lysozyme and insulin was investigated using a combination of different experimental techniques. Thioflavin T fluorescence assay and atomic force microscopy were applied for monitoring of disaggregation activity of fullerenes. It was demonstrated that both types of fullerene-based complexes are very effective in disassembling preformed fibrils, and characterized by the low apparent half-maximal disaggregation concentration (DC50) in the range of ∼22–30 μg mL–1. Small-angle neutron scattering was employed to monitor the different stages of the disassembly process with respect to the size and morphology of the aggregates. Based on the obtained results, a possible disassembly mechanism for amyloid fibrils interacting with fullerene/NMP complexes was proposed. The study is a principal step in understanding of the fullerenes destruction mechanism of the protein amyloids, as well as providing valuable information on how macromolecules can be engineered to disassemble unwanted amyloid aggregates by different mechanisms.

Background: Alzheimer’s disease is progressive neurodegenerative disease incidence of which has been steadily growing for past decades. Etiology of Alzheimer’s disease consists of multiple micro and macroscopic changes and to this day is not satisfactorily understood. Conventional therapy is based on inhibition of acetylcholinesterase of Alzheimer’s disease is connected with considerable worldwide expenses. Objective: Six clinically used cholinesterase inhibitors (donepezil, physostigmine, galanthamine, huperzine A, rivastigmine and tacrine) and memantine were compared according to their cholinesterase inhibitory properties. Additionally, the ability of tested compounds to directly inhibit protein aggregation as well as the capability to promote the protein amyloid fibrils depolymerization was determined. Method: Adopted colorimetric assay according to Ellman was used to evaluate the inhibition aktivity against cholinesterases. The ability of compounds to influence agregation inhibition and depolymerization activity was measured by means of thioflavin fluorescence assay. Results: Huperzine A was found to be the most potent, highly selective acetylcholinesterase inhibitor. Tacrine and physostigmine were the most potent butyrylcholinesterase inhibitors. Several inhibitors showed some weak potency to affect protein fibrils aggregation or depolymerization. Namely rivastigmine and galanthamine showed some effect on protein polymerization and depolymerization. Conclusion: Data provided by experiments suggest that clinically used and standard cholinesterase inhibitors influence the protein superstructures however the effect is weak. The need for novel structures of cholinesterase inhibitors with sufficient protein aggregation inhibition and/or depolymerization is evident.