Despite the wide variety of available cationic lipid platforms for the delivery of nucleic acids into cells, the optimization of their composition has not lost its relevance. The purpose of this work was to develop multi-component cationic lipid nanoparticles (LNPs) with or without a hydrophobic core from natural lipids in order to evaluate the efficiency of LNPs with the widely used cationic lipoid DOTAP (1,2-dioleoyloxy-3-[trimethylammonium]-propane) and the previously unstudied oleoylcholine (Ol-Ch), as well as the ability of LNPs containing GM3 gangliosides to transfect cells with mRNA and siRNA. LNPs containing cationic lipids, phospholipids and cholesterol, and surfactants were prepared according to a three-stage procedure. The average size of the resulting LNPs was 176 nm (PDI 0.18). LNPs with DOTAP mesylate were more effective than those with Ol-Ch. Core LNPs demonstrated low transfection activity compared with bilayer LNPs. The type of phospholipid in LNPs was significant for the transfection of MDA-MB-231 and SW 620 cancer cells but not HEK 293T cells. LNPs with GM3 gangliosides were the most efficient for the delivery of mRNA to MDA-MB-231 cells and siRNA to SW620 cells. Thus, we developed a new lipid platform for the efficient delivery of RNA of various sizes to mammalian cells.
Osteophytes (OPs) are a diagnostic hallmark of osteoarthritis (OA). However, the mechanisms underlying their initiation and their relationship with early subchondral bone changes remain poorly understood. Existing research primarily relies on animal models and late-stage OA tissue, leaving the initial morphological events leading to OP formation unclear. Background/Objectives: This study aimed to identify early changes in the subchondral bone as a key trigger for OP initiation in human OA through a comprehensive histological analysis of the subchondral area, including its peripheral regions. Methods: We conducted an extensive histological examination of full-section human tibial plateaus, including load-bearing and non-load-bearing compartments, obtained from patients with early and late stages of OA. Results: Our data demonstrate that subchondral bone changes, including osteoporosis, osteosclerosis, and microcracks, begin at the pre-chondropathic stage alongside microscopically intact cartilage. We identified a previously undescribed zone on the vertical wall of the tibial condyle (the VEPLS zone), characterized by reduced calcium content in the cortical plate and the persistence of embryonic cartilage, making it morphologically vulnerable. The first event in OP formation is microcracks in the cortical angle and the adjacent subchondral trabecula. These injuries initiate reparative osteogenesis, which, under continuous traumatic load (presumably shear forces due to joint instability), becomes insufficient, leading to cortical angle protrusion and OP formation. OP growth is accompanied by the deformation of the VEPLS zone cortical plate, causing vascular impairment and exacerbating bone weakness. Conclusions: Based on our findings, we propose the concept of tissue micro-instability. This concept posits that osteophytosis results from chronic microcracks and failed bone regeneration in vulnerable subchondral structures, induced by joint instability. We define an OP as a pathological outgrowth arising from this tissue micro-instability. Our study highlights the critical role of the peripheral subchondral area, particularly the VEPLS zone, in OA pathogenesis.
3 June 2025 in Russian Journal of Bioorganic Chemistry
The review is devoted to the physical methods of investigation of the structural characteristics of inclusion complexes of supramers of phospholipid derivatives of cyclodextrins. Phospholipid derivatives of cyclodextrins are formed by attaching a phospholipid moiety to the cyclodextrin molecule. This modification imparts additional structural features to the cyclodextrin, increasing its solubility and stability in aqueous media. These new compounds can self-assemble in aqueous media into supramolecular nanocomplexes of different types. Biomedical applications are envisaged for nanoencapsulation of drug molecules in hydrophobic interchain volumes and nanocavities of amphiphilic cyclodextrins (serving as drug carriers or pharmaceutical excipients), antitumor phototherapy, gene delivery, and protection of unstable active ingredients by the complexation of inclusions in nanostructured media. Special attention is focused on the morphology of nanoparticles, because efficient delivery systems must meet certain requirements. Classical physical methods cannot provide detailed information on the properties of potential structures for biomedical applications. To this end, the search for new noninvasive approaches is necessary.
The work presents the first results of a series of experiments on studying the mechanism of binding of microvesicles to a recipient cell using scanning fluorescence confocal microscopy. A new approach has been developed for visualizing the penetration of microvesicles into a cell.
23 November 2023 in Russian Journal of Bioorganic Chemistry
To date, the most common drug for diagnosis of cancer tumors is [18F]-fluorodeoxyglucose, a radiopharmaceutical for positron emission tomography, which utilizes an increased glucose metabolism by cancer cells. At the same time, the approach based on glucose derivatives is not applicable in some cases. Inflammatory or other benign processes are often indistinguishable from tumors when the tumor is not specific to glucose, i.e., not only the malignant but also healthy cells actively consume [18F]-fluorodeoxyglucose. In these cases, it is necessary to utilize other metabolic pathways, which can be specific to radiopharmaceuticals for a specific tumor in a given organ.
To date, the most common drug for the diagnosis of cancer tumors is [18F]-fluorodeoxyglucose, an radiopharmaceuticals for positron emission tomography diagnostics using the fact of increased glucose metabolism by cancer cells. At the same time, there are a number of cases where an approach based on glucose derivatives is not applicable. In many cases, inflammation or other benign processes are indistinguishable from tumor formations. For such cases of non-specificity of oncologies to glucose (not only tumor cells, but also healthy cells actively consume [18F]-fluorodeoxyglucose), the use of other metabolic pathways is required, which, in the case of a specific tumor in this organ, will be specific to the radiopharmaceuticals used.