Upconverting nanoparticles (UCNPs) have attracted much attention in nanomedicine due to their ability to upconvert photons. However, their adverse effects hinder the biomedical applications. In this paper, bisphosphonate-modified poly(isobutylene-alt-maleicacid)-graft-poly(N,N-dimethylacrylamide)-coated NaYF4:Yb,Er,Pr UCNPs (UCNP@PIMAPDMA) nanoparticles were designed, which exhibited luminescence emission simultaneously in the visible and NIR-II regions. The developed UCNPs were characterized by a range of physicochemical methods, including transmission electron and energy dispersive microscopy (TEM and EDAX), dynamic light scattering (DLS), X-ray diffraction analysis (XRD), spectrofluorometry, X-ray photoelectron spectroscopy (XPS), and so forth. The UCNP@PIMAPDMA nanoparticles were also evaluated in cell cultures and experimental animals. The particles showed good biocompatibility with cultured human embryonic kidney HEK293 cells commonly used in toxicological studies. Neat UCNPs were cytotoxic towards these cells, which was confirmed by measuring their viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Blood serum proteins adhered to the surface of UCNP@PIMAPDMA particles, forming a protein corona that may contribute to particle biosafety. After intravenous injection of these particles into laboratory mice, there were no statistically significant changes in body mass of the treated animals. Also, no big adverse effects on blood cell profile, enzymatic and metabolic markers of hepatotoxicity and nephrotoxicity were observed. Finally, the application potential of UCNP@PIMAPDMA nanoparticles was confirmed by successfully imaging the cytoplasm of rat mesenchymal stem cells and rat C6 glioblastoma cells using laser scanning confocal microscopy.

Keywords: cytotoxicity | hematology parameters | polymer coating | protein corona | upconverting nanoparticles

UDC: 616.94:576.8.06:616.155.34:616.155.321]-002.828-092.9

   Background. Sepsis is a major global health problem, with fungal pathogens such as Candida albicans emerging as a significant cause of invasive infection. Fungal sepsis has a higher mortality rate than bacterial sepsis and is complicated by antifungal resistance. Although neutrophil extracellular traps (NETs) help to contain fungi, excessive NETs can contribute to inflammation and tissue injury. Understanding these mechanisms could reveal markers of disease activity and new therapeutic targets. Materials and Methods. Fungal sepsis was induced in twelve male BALB/c mice via an intraperitoneal injection of Meyerozyma guilliermondii (107 cells per mouse). Blood was collected at the beginning of the study and then on days 1–3, 7–9, and 13–15. Serum was analyzed for IgG, IgM, circulating immune complexes (ELISA), and extracellular DNA (fluorescence assay). 
   Results and Discussion. In mice with fungal sepsis, IgG levels remained stable while IgM levels increased significantly between days 7 and 9, before declining from day 13. IgG–IgM immune complexes peaked around days 8–9, reflecting active antigenantibody responses. Free DNA levels, which indicate NETs formation, increased by day 7 and then declined, showing early neutrophil activation followed by humoral control. Together, these findings suggest a coordinated immune response in which NETs and immune complexes contribute to both pathogen control and inflammation.
   Conclusion. Fungal sepsis induced by Meyerozyma guilliermondii resulted in early NETosis and an increase in IgM and immune complexes. IgM levels peaked on days 7–9 before declining. Unlike Candida albicans, this strain does not cause rapid lethality, enabling detailed tracking of disease progression over time. After day 9, immune parameters began to normalize, indicating the resolution of the acute phase and supporting the usefulness of this model for studying host immune dynamics in fungal sepsis.
   Keywords: fungal sepsis, Meyerozyma guilliermondii, acute inflammation, immune defense, circulating immune complexes, neutrophil extracellular traps
(NETs)

 Applied Nanoscience 

Abstract

The biocompatibility of NPs to blood cells is a key issue when these NPs are planned for intravenous application because of potential contact with blood cells and proteins. In this work, γ-Fe₂O₃ NPs (~ 9 nm) and their poly(N,N-dimethylacrylamide) (PDMA) and SiO₂-coated derivatives (γ-Fe₂O₃@PDMA and γ-Fe₂O₃@SiO₂, respectively) were investigated. It was detected that both PDMA and SiO₂ coatings decreased NPs’ aggregation in the buffer solutions, as well as in cell culture medium. Neither neat γ-Fe₂O₃ NPs nor their coated derivatives possessed hemolytic activity toward red blood cells. There was no significant loss of body weight observed after the intravenous injection to laboratory mice. The immune response to the injected NPs was assessed by the ELISA measuring. No antibodies of the IgM class were detected, which suggests lack of acute inflammation. On the 35th day of the experiment, there was a rise in the content of the anti-OVA IgG noticed in all three types of the NPs; however, this rise was lower compared to that induced by the positive control. The injected NPs were found to be spread and settled in the pouch cavity, and none of the tested NPs caused vascular damage or distinct signs of inflammation. Summarizing, γ-Fe₂O₃ NPs coated with the PDMA or SiO₂ manifested good compatibility with blood cells in in vitro and in vivo investigations.

Keywords Maghemite · Nanoparticles · Poly(N,N-dimethylacrylamide) · Silica · Hemolytic action · Immune response

The effects of natural clinoptilolite originated from the Transcarpathian region in the Western Ukraine and its composites doped with metal ions were studied toward: (1) cultured pseudo-normal mammalian cell and murine macrophages; (2) neutrophils of blood of healthy human donors; (3) mice immunized with model antigen; (4) mice under air-pouch model for estimation of microvasculature damage; (5) Candida albicans fungi. Silver doping enhanced cytotoxic action of natural clinoptilolite, while zinc doping did not do that. Clinoptilolite-Ag(NH₃)²⁺ was non-toxic for murine macrophages and moderately toxic for human HEК293 cells. Toxicity of clinoptilolite-Ag⁺ composite toward HEК293 cells was comparable with the effect in positive control. Natural clinoptilolite and its silver derivatives enhanced the humoral immune response in mice and the levels of antibodies were comparable with such levels at response to standard adjuvant, which, however, damaged the microvasculature in mice. Furthermore, natural and Ag-enriched clinoptilolite were capable of activating neutrophils with a release of neutrophil extracellular traps. Finally, we showed that both clinoptilolite-Ag(NH₃)²⁺ and clinoptilolite-Ag+ possessed much higher antifungal activity toward Candida albicans compared to such activity of the nonmodified clinoptilolite, while their doping with zinc did not show such enhancement. Thus, the Transcarpathian clinoptilolite possesses low toxicity toward mammalian cells and activates neutrophils in vitro, while silver doping enhanced the cytotoxicity of this material. Silver-doped derivatives demonstrated stimulating action on antibody production and the antifungal effect. Thus, the developed clinoptilolite-based composites are perspective for use as novel natural immuno-stimulators and antifungal agents.

 Keywords Clinoptilolite · Cytotoxicity · Immune-stimulation · Antifungal activity

Abstract: Searching for new types of biological activities among preliminarily identified hit compounds is a key challenge in modern medicinal chemistry. In our study, a previously studied 3-[5-(1H-indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl]-propionic acid (Les-6614) was screened for antimicrobial, antifungal, anti-allergic and antitumor activities. Moreover, cytotoxicity, molecular docking, and, the SwissAdme online target screening were accomplished. It was determined that the Les-6614 has slight antimicrobial and antitumor activity. However, the studied compound decreased IgE levels in sensitized guinea pigs by 33-86% and reduced IgA, IgM, IL-2, and TNF-α, indicating anti-inflammatory and anti-allergic activities. According to the SwissADME web tool, target predictions Les-6614 potentially has an affinity for Lysosomal protective protein, Thromboxane-A synthase, and PPARγ. The molecular docking confirmed that the studied 2-thioxo-4-thiazolidinone derivative showed good bonding with LLP and TXAS leading to stable protein-ligand complexes. Also, the Les-6614 is a potential PPARγ modulator, which is important in the pathogenesis of allergy, cancer, and cardiovascular diseases.