Preparation of UiO-66 loaded Letrozole nano-drug delivery system: enhanced anticancer and apoptosis activity.

The use of drug delivery systems in targeting and achieving the targeting of drugs in treating diseases, especially cancer, has attracted the attention of researchers. Letrozole is one of the drugs for the treatment of breast cancer. In this study, the organic-metallic pharmaceutical porous nanostructure based on zirconium UiO-66 loaded letrozole was synthesized. Its cytotoxicity and effect on apoptosis and migration against breast cancer cell line were investigated. In this experimental study, the UiO-66 nanoparticle-loaded letrozole was synthesized using zirconium chloride (ZrCl4), dimethylformamide (DMF), and HCl. Its characteristics were determined by scanning electron microscopy, and its average size was determined by the DLS method. Also, the rate of letrozole drug release from the nanoparticle was investigated in 24, 48, and 72 h. In addition, its cytotoxicity effects were investigated using the MTT colorimetric method at concentrations of 3.125-100 µg/ml against the breast cancer cell line (MCF-7) in the periods of 48 and 72 h. Also, the expression level of apoptotic genes Bax and Bcl2 was investigated by the Real-Time PCR method. Also, the amount of cell migration was done by the migration assay method. The results showed that UiO-66 bound to letrozole had a spherical morphology and an average size of 9.2 ± 160.1. Also, the letrozole drug was loaded by 62.21 ± 1.80% in UiO-66 nanoparticles and had a slower release pattern than free letrozole in the drug release test, so within 72 h, 99.99% of free letrozole was released in If in UiO-66 containing letrozole, 57.55% of the drug has been released. Also, the cytotoxicity results showed that UiO-66 bound to letrozole has more significant cytotoxic effects than free letrozole (p < 0.05). Also, the results of Bax and Bcl2 gene expression showed that the treatment of MCF-7 cells with UiO-66 nanoparticles attached to letrozole increased the expression of Bax and Bcl2 genes compared to the reference gene Beta-actin in MCF-7 cell line, respectively. (p < 0.05) increased by 3.71 ± 0.42 and (p < 0.01) decreased by 0.636 ± 0.034 (p < 0.05). Cell migration results showed that the concentration of 50 µg/ml of UiO-66 bound to letrozole decreased the migration of MCF-7 cells. Generally, the results of this study showed that UiO-66 loaded letrozole can be used as a suitable drug carrier for cellular purposes, as it has increased the effects of cytotoxicity and the rate of apoptosis in breast cancer cell line (MCF-7), so it can be used with more studies used nanocarriers as a drug delivery system.

A model to improve user acceptance of e-services in healthcare systems based on technology acceptance model: an empirical study.

Improving the quality of electronic services (e-services) is essential when dealing with unforeseen factors and uncertainties in healthcare, such as the outbreak of coronavirus (COVID-19) and changes in the needs and expectations of patients. This paper presents a comprehensive conceptual model in healthcare systems for improving the user acceptance of e-services. A model referred to as the technology acceptance model (TAM) is considered that includes several factors. The factors are computer literacy, website quality, service quality, user attitude, perceived enjoyment, and user satisfaction. According to the collected data and the performed analysis, the fit indices of this survey reveal that the conceptual model has an acceptable fit. The findings are as follows. Computer literacy has positive effects on perceived enjoyment and ease of use. Website quality has positive effects on perceived enjoyment, ease of use, and user satisfaction. Perceived enjoyment has a positive effect on perceived usefulness. Ease of use has positive effects on the usefulness, willingness to use e-services, and user attitude. User satisfaction has a positive effect on user attitude. Perceived usefulness has a positive effect on the willingness to use e-services. Finally, among these variables, only the user attitude has no significant effect on the willingness to use e-services in the healthcare system. Therefore, to promote performance quality and to motivate people to use e-services, healthcare managers should improve these factors.

Differential toxicity of processed and non-processed states of CoCrMo degradation products generated from a hip simulator on neural cells.

Physico-chemical characteristics of the CoCrMo degradation products have played an important role in cytotoxicity and clinical complications on the orthopedic patients who have metal implants. Previous studies have limited reflection on the physicochemical characteristics of the degradation products generated in vivo, which are very different from individual metal particles and/or ions obtained from different commercial sources. In this study, we aimed to understand the differences in toxicity induced by the degradation products in as-synthesized form as well as those obtained after post-processing. The degradation products were generated using a hip-simulator by maintaining physiological conditions closer to in vivo and separated into two batches, one with processing by washing and drying called processed degradation products (PDP) and another batch as 'as-synthesized' degradation product (DP). We studied the dose-dependent toxicity response by neural cells derived from induced pluripotent stem cells. The results of the study show that as-synthesized DPs are more toxic to neural cells even at lower concentrations studied with evident low TC50 (1-5 µg/ml) concentrations compared to PDP (25 µg/ml). Flow cytometric analysis showed a significant (p<.01) increase in uptake of the particles after 24 h and corresponding ROS production in DP-treated cells. RT-PCR analysis of oxidative specific gene expression showed, elevated mRNA levels of NADPH oxidase-1, nuclear transcription factor, superoxide dismutase-2 and glutaredoxin-2 in DP-treated cells after 6 h. The results of the study provided a clear evidence of the differential response of neural cells on the degradation products as a function of concentrations and their chemical nature.

Bio-camouflage of anatase nanoparticles explored by in situ high-resolution electron microscopy.

While titanium is the metal of choice for most prosthetics and inner body devices due to its superior biocompatibility, the discovery of Ti-containing species in the adjacent tissue as a result of wear and corrosion has been associated with autoimmune diseases and premature implant failures. Here, we utilize the in situ liquid cell transmission electron microscopy (TEM) in a liquid flow holder and graphene liquid cells (GLCs) to investigate, for the first time, the in situ nano-bio interactions between titanium dioxide nanoparticles and biological medium. This imaging and spectroscopy methodology showed the process of formation of an ionic and proteic bio-camouflage surrounding Ti dioxide (anatase) nanoparticles that facilitates their internalization by bone cells. The in situ understanding of the mechanisms of the formation of the bio-camouflage of anatase nanoparticles may contribute to the definition of strategies aimed at the manipulation of these NPs for bone regenerative purposes.