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.

Topography mapping enables the analysis of the surface properties of nanocarriers relevant for drug delivery systems.

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.

Cyclodextrin-functionalized micelles were studied using TEM, SAXS, and molecular dynamics simulations. Topography analysis showed clustering and low mobility of CDs, highlighting structural features important for optimizing nanoparticle drug delivery.

Synthetic glycolipids and similar amphiphils with peptide and other head groups have been designed for labeling/modification of living cells under mild physiological conditions. Under-standing the mechanism of their penetration through the cellular glycocalyx and subsequent insertion into the plasma membrane opens up the prospect of improving the recently found anti-tumor properties of such constructs. In this work, we applied small-angle X-ray scattering (SAXS) technique to characterize structure of nanoparticles formed by self-assembly of synthetic glycolipid A (type 2)-Ad-DE and to estimate its dependence on the glycolipid concentration. The studies were performed at a range of SAXS-applicable concentrations. The obtained results indicate that self-assembly process leads to formation of monodisperse nanoparticles with micelle-like architecture, which is maintained regardless of concentration, indicating absence of the nanoparticle’s positive interaction with their glycopart. We applied ab initio modeling that showed a good agreement with experimental data, and found that the ellipsoid monodisperse nanoparticles have a size of about 14 nm. Quasi-atomic modeling visualised that glycan ligands are well accessed for biological recognition. This knowledge will facilitate further study of the formation of the supramolecular form(s) of A(type 2)-Ad-DE and other glycolipids within the glycocalyx and its further fate in new therapeutic strategies.