Zinc oxide nanoparticles (ZnO NPs) were obtained by the microwave solvothermal synthesis (MSS) method. The precursor of the MSS reaction was a solution of hydrated zinc acetate in ethylene glycol with water addition. It was proved that by controlling the water concentration in the precursor it was possible to control the size of ZnO NPs in a programmed manner. The less the water content in the precursor, the smaller the size of ZnO NPs obtained. The obtained NPs with the average particle size ranging from 25 nm to 50 nm were characterised by homogeneous morphology and a narrow distribution of particle sizes. The following parameters of the obtained ZnO NPs were determined: pycnometric density, specific surface area, phase purity, chemical composition, lattice parameters, average particle size, and particle size distribution. The average size of ZnO NPs was determined using Scherrer’s formula, Nanopowder XRD Processor Demo web application, by converting the results of the specific surface area, and TEM tests using the dark field technique. ZnO morphology and structure were determined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The test performed by the X-ray powder diffraction (XRD) confirmed that crystalline ZnO, pure in terms of phase, had been obtained.
Ectosomes (Ects) are a subpopulation of extracellular vesicles formed by the process of plasma membrane shedding. In the present study, we profiled ectosome-specific microRNAs (miRNAs) in patients with type 2 diabetes mellitus (T2DM) and analyzed their pro- and anti-angiogenic potential.Methods: We used different approaches for detecting and enumerating Ects, including atomic force microscopy, cryogenic transmission electron microscopy, and nanoparticle tracking analysis. Furthermore, we used bioinformatics tools to analyze functional data obtained from specific miRNA enrichment signatures during angiogenesis and vasculature development.Results: Levels of miR-193b-3p, miR-199a-3p, miR-20a-3p, miR-26b-5p, miR-30b-5p, miR-30c-5p, miR-374a-5p, miR-409-3p, and miR-95-3p were significantly different between Ects obtained from patients with T2DM and those obtained from healthy controls.Conclusion: Our results showed differences in the abundance of pro- and anti-angiogenic miRNAs in Ects of patients with T2DM, and are suggestive of mechanisms underlying the development of vascular complications due to impaired angiogenesis in such patients.
Naturally derived prodrugs have a wide range of pharmacological activities, including anticancer, antioxidant, and antiviral effects. However, significant barriers inhibit their use in medicine, e.g. their hydrophobicity. In this comprehensive study, we investigated simple and effective nanoformulations consisting of amine-functionalized and conjugated with folic acid (FA) mesoporous silica nanoparticles (MSNs). Two types of MSNs were studied: KCC- 1, with mean size 324 nm and mean pore diameter 3.4 nm, and MCM - 41, with mean size 197 and pore diameter 2 nm. Both types of MSNs were loaded with three anticancer prodrugs: curcumin, quercetin, and colchicine. The nanoformulations were tested to target in vitro human hepatocellular carcinoma cells (HepG2) and HeLa cancer cells. The amine-functionalized and FA-conjugated curcumin-loaded, especially KCC-1 MSNs penetrated all cells organs and steadily released curcumin. The FA-conjugated MSNs displayed higher cellular uptake, sustained intracellular release, and cytotoxicity effects in comparison to non-conjugated MSNs. The KCC-1 type MSNs carrying curcumin displayed the highest anticancer activity. Apoptosis was induced through specific signaling molecular pathways (caspase-3, H2O2, c-MET, and MCL-1). The nanoformulations displayed also an enhanced antioxidant activity compared to the pure forms of the prodrugs, and the effect depended on the time of release, type of MSN, prodrug, and assay used. FA-conjugated MSNs carrying curcumin and other safe natural prodrugs offer new possibilities for targeted cancer therapy.
Antimitotics are important anticancer agents and include the natural alkaloid prodrug colchicine (COL). However, a major challenge of using COL as an anticancer drug is its cytotoxicity. We developed a novel drug delivery system (DDS) for COL using mesoporous silica nanoparticles (MSNs). The MSNs were functionalized with phosphonate groups, loaded with COL, and coated with folic acid chitosan-glycine complex. The resulting nanoformulation, called MSNsPCOL/CG-FA, was tested for action against cancer and normal cell lines. The anticancer effect was highly enhanced for MSNsPCOL/CG-FA compared to COL. In the case of HCT116 cells, 100% inhibition was achieved. The efficiency of MSNsPCOL/CG-FA ranked in this order: HCT116 (colon cancer) > HepG2 (liver cancer) > PC3 (prostate cancer). MSNsPCOL/CG-FA exhibited low cytotoxicity (4%) compared to COL (~60%) in BJ1 normal cells. The mechanism of action was studied in detail for HCT116 cells and found to be primarily intrinsic apoptosis caused by an enhanced antimitotic effect. Furthermore, a contribution of genetic regulation (metastasis-associated lung adenocarcinoma transcript 1 (MALAT 1), and microRNA (mir-205)) and immunotherapy effects (angiopoietin-2 (Ang-2 protein) and programmed cell death protein 1 (PD-1) was found. Therefore, this study shows enhanced anticancer effects and reduced cytotoxicity of COL with targeted delivery compared to free COL and is a novel method of developing cancer immunotherapy using a low-cost small-molecule natural prodrug.
SummaryThe correlation between density and specific surface area of ZrO2 nanoparticles (NPs) was studied. The NPs were produced using a hydrothermal process involving microwave heating. The material was annealed at 1100 °C which resulted in an increase in the average grain size of the ZrO2 NPs from 11 to 78 nm and a decrease in the specific surface area from 97 to 15 m2/g. At the same time, the density increased from 5.22 g/m3 to 5.87 g/m3. This effect was interpreted to be the result of the presence of a hydroxide monolayer on the NP surface. A smaller ZrO2 grain size was correlated with a larger contribution of the low density surface layer to the average density. To prove the existence of such a layer, the material was synthesized using 50% heavy water. Fourier transform infrared spectroscopy (FTIR) permitted the identification of the –OD groups created during synthesis. It was found that the –OD groups persisted on the ZrO2 surface even after annealing at 1100 °C. This hydroxide layer is responsible for the decrease in the average density of the NPs as their size decreases. This study of the correlation between particle size and density may be used to assess the quality of the NPs. In most cases, the technological aim is to avoid an amorphous layer and to obtain fully crystalline nanoparticles with the highest density possible. However, due to the effect of the surface layers, there is a maximum density which can be achieved for a given average NP diameter. The effect of the surface layer on the NP density becomes particularly evident for NPs smaller than 50 nm, and thus, the density of nanoparticles is size dependent.
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