Aleksei N. Smirnov

Purinergic P2X receptors have a wide distribution within the body and modulate a number of physiological processes, being also involved in the development and progression of inflammation-, neuroinflammation-, neurodegeneration-, and cancer-related diseases. Radioligands that can detect specific P2X receptor subtypes and reveal their level of expression are of key importance for the development of novel P2X modulators, for the depiction of the involvement of these proteins in physio-pathological processes, and for the availability of novel diagnostic tools to be used for imaging experiments in vivo. Here we review and summarise the various P2X-targeting radioligands developed and reported to date, ranging from analogues of the endogenous P2X agonist ATP to the more recent and P2X subtype-selective allosteric modulators. Many of the high-affinity radioligands described are only suitable as in vitro receptor probes. No viable P2X3 or P2X4 radioligands for in vivo positron emission tomography (PET) imaging have been developed and reported to date. However, P2X7 antagonists, such as [¹¹C]SMW139, [¹¹C]GSK1482160, [¹¹C]JNJ-54173717, and [¹⁸F]JNJ-64413739, have been successfully applied to PET imaging in the brain.

Natural and renewable sources of calcium carbonate (CaCO₃), also referred to as “biogenic” sources, are being increasingly investigated, as they are generated from a number of waste sources, in particular those from the food industry. The first and obvious application of biogenic calcium carbonate is in the production of cement, where CaCO₃ represents the raw material for clinker. Overtime, other more added-value applications have been developed in the filling and modification of the properties of polymer composites, or in the development of biomaterials, where it is possible to transform calcium carbonate into calcium phosphate for the substitution of natural hydroxyapatite. In the majority of cases, the biological structure that is used for obtaining calcium carbonate is reduced to a powder, in which instance the granulometry distribution and the shape of the fragments represent a factor capable of influencing the effect of addition. As a result of this consideration, a number of studies also reflect on the specific characteristics of the different sources of the calcium carbonate obtained, while also referring to the species-dependent biological self-assembly process, which can be defined as a more “biomimetic” approach. In particular, a number of case studies are investigated in more depth, more specifically those involving snail shells, clam shells, mussel shells, oyster shells, eggshells, and cuttlefish bones.

Cyanine dyes are widely used in various techniques of bioimaging. The development of new types of optical tags with cyanine dyes combined with plasmonic nanoparticles is of great interest. In this work, surface-enhanced Raman scattering (SERS) study of optical behavior of cyanines adsorbed on gold nanoparticles in suspensions is presented to predict the optical response of corresponding tags. Two dyes, sulfo-cyanine 5.5 NHS ester and sulfo-cyanine 7.5 NHS ester were considered as they are suitable for the first transparency window of biological tissues. Gold nanoparticles of anisotropic shape were used as a plasmonic substrate. The assignment of bands in SERS spectra of both dyes was performed based on DFT calculations of vibrational frequencies of the molecules. The adsorption of dyes on the nanoparticles with different surface charges was studied. Spectral changes showed that a reorientation of the molecules occurs and reactive NHS ester tail is more accessible sterically in the case of a positive surface charge. The effect of aggregation-induced agent on the SERS response of sulfo-cyanines was also studied. Addition of chloride anions led to about five-fold increase of SERS intensity for sulfo-cyanine 5.5 NHS ester.

Currently, the number of patients with neurodegenerative pathologies is estimated at over one million, with consequences also on the economic level. Several factors contribute to their development, including overexpression of A_2A adenosine receptors (A_2AAR) in microglial cells and up-regulation and post-translational alterations of some casein kinases (CK), among them, CK-1δ. The aim of the work was to study the activity of A_2AAR and CK1δ in neurodegeneration using in-house synthesized A_2A/CK1δ dual anta-inhibitors and to evaluate their intestinal absorption. Experiments were performed on N13 microglial cells, which were treated with a proinflammatory CK cocktail to simulate an inflammatory state typical of neurodegenerative diseases. Results showed that the dual anta-inhibitors have the ability to counteract the inflammatory state, even if compound 2 is more active than compound 1. In addition, compound 2 displayed an important antioxidant effect similar to the reference compound ZM241385. Since many known kinase inhibitors are very often unable to cross lipid bilayer membranes, the ability of A_2A/CK1δ double anta-inhibitors to cross the intestinal barrier was investigated by an everted gut sac assay. HPLC analysis revealed that both compounds are able to cross the intestinal barrier, making them promising candidates for oral therapy.

Anisotropic gold nanoparticles have been recognized as promising agents for medical diagnostics and cancer therapy due to their wide functionality, photothermal effect, and ability for optical signal amplification in the near-infrared range. In this work, a simple and rapid method for the preparation of bone-shaped gold nanoparticles coated with a dye-impregnated silica shell with an aminated surface is proposed. The possibility of further functionalization the nanostructures with a delivery vector using folic acid as an example is demonstrated. The average size of the resulting tags does not exceed 70 nm, meeting the criteria of cell endocytosis. The prepared tags exhibit surface-enhanced Raman scattering (SERS) spectra at excitation with lasers of 632.8 and 785 nm. Cell imaging is performed on HeLa cells based on the most pronounced SERS bands as a tracking signal. The obtained images, along with scanning electron microscopy of cell samples, revealed the tendency of tags to agglomerate during endocytosis followed by the “hot spots” effect. To evaluate the toxic and proliferative effect of the nanotags, an MTT assay was performed with two HeLa and HEP G2 cell lines. The results revealed higher viability for HEP G2 cells.

The nanocrystalline phosphor NaGd_0.7Eu_0.3F₄ with the most intensive luminescence among NaGd_1–xEu_xF₄ (x = 0–1) compounds was obtained by hydrothermal synthesis. The unit cell parameters and nanoparticle size were determined. The cytotoxicity, luminescent, and magnetic properties were characterized.

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