Super Magnetic Niosomal Nanocarrier as a New Approach for Treatment of Breast Cancer: A Case Study on SK-BR-3 and MDA-MB-231 Cell Lines

In the present study, a magnetic niosomal nanocarrier for co-delivery of curcumin and letrozole into breast cancer cells has been designed. The magnetic NiCoFe₂O₄ core was coated by a thin layer of silica, followed by a niosomal structure, allowing us to load letrozole and curcumin into the silica layer and niosomal layer, respectively, and investigate their synergic effects on breast cancer cells. Furthermore, the nanocarriers demonstrated a pH-dependent release due to the niosomal structure at their outer layer, which is a promising behavior for cancer treatment. Additionally, cellular assays revealed that the nanocarriers had low cellular uptake in the case of non-tumorigenic cells (i.e., MCF-10A) and related high viability but high cellular uptake in cancer cell lines (i.e., MDA-MB-231 and SK-BR-3) and related low viability, which is evidenced in their high cytotoxicity against different breast cancer cell lines. The cytotoxicity of the letrozole/curcumin co-loaded nanocarrier is higher than that of the aqueous solutions of both drugs, indicating their enhanced cellular uptake in their encapsulated states. In particular, NiCoFe₂O₄@L-Silica-L@C-Niosome showed the highest cytotoxicity effects on MDA-MB-231 and SK-BR-3 breast cancer cells. The observed cytotoxicity was due to regulation of the expression levels of the studied genes in breast cancer cells, where downregulation was observed for the Bcl-2, MMP 2, MMP 9, cyclin D, and cyclin E genes while upregulation of the expression of the Bax, caspase-3, and caspase-9 genes was observed. The flow cytometry results also revealed that NiCoFe₂O₄@L-Silica-L@C-Niosome enhanced the apoptosis rate in both MDA-MB-231 and SK-BR-3 cells compared to the control samples. The findings of our research show the potential of designing magnetic niosomal formulations for simultaneous targeted delivery of both hydrophobic and hydrophilic drugs into cancer cells in order to enhance their synergic chemotherapeutic effects. These results could open new avenues into the future of nanomedicine and the development of theranostic agents.     

Local Insulin-Derived Amyloidosis Model Confronted with Silymarin: Histological Insights and Gene Expression of MMP,TNF-α, and IL-6

Amyloidosis is a heterogeneous group of protein deposition diseases associated with the presence of amyloid fibrils in tissues. Analogs of insulin that are used for treating diabetic patients (including regular insulin) can form amyloid fibrils, both in vitro and in vivo as reported in patients. The main purpose of this study was the induction of localized insulin-generated amyloidosis and the observation of silymarin effects on this process. In order to obtain amyloid structures, regular insulin was incubated at 37 °C for 24 h. Congo red absorbance and transmission electron microscopy images validated the formation of amyloid fibrils. Those fibrils were then injected subcutaneously into rats once per day for 6, 12 or 18 consecutive days in the presence or absence of silymarin, and caused development of firm waxy masses. These masses were excised and stained with Hematoxylin and Eosin, Congo red and Thioflavin S. Histological examination showed adipose cells and connective tissue in which amyloid deposition was visible. Amyloids decreased in the presence of silymarin, and the same effect was observed when silymarin was added to normal insulin and injected subsequently. Furthermore, plasma concentrations of MMP2, TNF-α, and IL-6 inflammatory factors were measured, and their gene expression was locally assessed in the masses by immunohistochemistry. All three factors increased in the amyloidosis state, while silymarin had an attenuating effect on their plasma levels and gene expression. In conclusion, we believe that silymarin could be effective in counteracting insulin-generated local amyloidosis.     

A Reinforcement Learning Based Routing in Cognitive Radio Networks for Primary Users with Multi-stage Periodicity

Wireless Personal Communications - Designing an efficient routing protocol for cognitive radio networks is critical due to the dynamic behavior of the primary users. Based on empirical studies, the...     

On the analysis of reputation for agent-based web services

Maintaining sound reputation requires robust control and investigation. In this paper, we analyze a reputation mechanism that objectively maintains accurate reputation evaluation of selfish agent-based web services. In the proposed framework, web services are ranked using their reputation as a result of provided feedback reflecting consumers’ satisfaction. However, selfish web services may alter their public reputation level by managing to get fake feedback. We investigate the payoffs of different scenarios by focusing on the issues that discourage web services to act maliciously. We also analyze the details of the proposed mechanism by discussing simulation and empirical results that fully depict the system parameters and show the feasibility of the proposed approach.     

A Hierarchical 3D Nanostructured Microfluidic Device for Sensitive Detection of Pathogenic Bacteria

Efficient capture and rapid detection of pathogenic bacteria from body fluids lead to early diagnostics of bacterial infections and significantly enhance the survival rate. We propose a universal nano/microfluidic device integrated with a 3D nanostructured detection platform for sensitive and quantifiable detection of pathogenic bacteria. Surface characterization of the nanostructured detection platform confirms a uniform distribution of hierarchical 3D nano‐/microisland (NMI) structures with spatial orientation and nanorough protrusions. The hierarchical 3D NMI is the unique characteristic of the integrated device, which enables enhanced capture and quantifiable detection of bacteria via both a probe‐free and immunoaffinity detection method. As a proof of principle, we demonstrate probe‐free capture of pathogenic Escherichia coli (E. coli) and immunocapture of methicillin‐resistant‐Staphylococcus aureus (MRSA). Our device demonstrates a linear range between 50 and 10⁴ CFU mL^?1, with average efficiency of 93% and 85% for probe‐free detection of E. coli and immunoaffinity detection of MRSA, respectively. It is successfully demonstrated that the spatial orientation of 3D NMIs contributes in quantifiable detection of fluorescently labeled bacteria, while the nanorough protrusions contribute in probe‐free capture of bacteria. The ease of fabrication, integration, and implementation can inspire future point‐of‐care devices based on nanomaterial interfaces for sensitive and high‐throughput optical detection.     

Adsorption of cerium and lanthanum from aqueous solutions by chitosan/polyvinyl alcohol/3-mercaptopropyltrimethoxysilane beads in batch and fixed-bed systems

Adsorption of La(III) and Ce(III) from aqueous solutions by novel chitosan modified with poly(vinyl alcohol) as a promoter of mechanical and chemical properties and 3-mercaptopropyltrimethoxysilane as a promoter of the functional group was investigated in batch and continuous modes. The FTIR analyses showed that mecapto groups have been successfully added to chitosan/poly(vinyl alcohol). The BET surface area, pore diameter, and pore volume of adsorbents were 1.68?m² g^?1, 2.516?nm, and 0.058?cm³ g^?1, respectively. The effects of the operating parameters such as pH, contact time, initial metal ion concentration, adsorbent dosage, and temperature were studied in batch mode operation. Optimum pH was found to be 5. According to the Langmuir model, the maximum adsorption capacities for La(III) and Ce(III) ions were 263.16 and 251.41?mg?g^?1, respectively. The thermodynamic study showed that the adsorption process of both metal ions was endothermic and spontaneous favored at the higher temperature. In the column study, the effects of the flow rate and initial concentration were investigated. The maximum adsorption capacities based on the Thomas model for La(III) and Ce(III) ions were 460.94 and 374.83?mg?g^?1 at a flow rate of 4?mL min^?1 and an initial metal concentration of 300?mg?L^?1, respectively.     

Multifunctional Nano‐Biointerfaces: Cytocompatible Antimicrobial Nanocarriers from Stabilizer‐Free Cubosomes

The rational design of alternative antimicrobial materials with reduced toxicity toward mammalian cells is highly desired due to the growing occurrence of bacteria resistant to conventional antibiotics. A promising approach is the design of lipid‐based antimicrobial nanocarriers. However, most of the commonly used polymer‐stabilized nanocarriers are cytotoxic. Herein, the design of a novel, stabilizer‐free nanocarrier for the human cathelicidin derived antimicrobial peptide LL‐37 that is cytocompatible and promotes cell proliferation for improved wound healing is reported. The nanocarrier is formed through the spontaneous integration of LL‐37 into novel, stabilizer‐free glycerol mono‐oleate (GMO)‐based cubosomes. Transformations in the internal structure of the cubosomes from Pn3m to Im3m‐type and eventually their transition into small vesicles and spherical micelles are demonstrated upon the encapsulation of LL‐37 into their internal bicontinuous cubic structure using small angle X‐ray scattering, cryogenic transmission electron microscopy, and light scattering techniques. Additional in vitro biological assays show the antimicrobial activity of the stabilizer‐free nano‐objects on a variety of bacteria strains, their cytocompatibility, and cell‐proliferation enhancing effect. The results outline a promising strategy for the comprehensive design of antimicrobial, cytocompatible lipid nanocarriers for the protection and delivery of bioactive molecules with potential for application as advanced wound healing materials.     

Ultraselective Carbon Nanotubes for Photoacoustic Imaging of Inflamed Atherosclerotic Plaques

Disruption of vulnerable atherosclerotic plaques often leads to myocardial infarction and stroke, the leading causes of morbidity and mortality in the United States. A diagnostic method that detects early-stage high-risk atherosclerotic plaques could prevent these sequelae. The abundant immune cells in the arterial wall, especially inflammatory Ly-6C^hi monocytes and foamy macrophages, are indicative of plaque inflammation, and may be associated with plaque vulnerability. Hence, a new method is sought to develop that specifically targets these immune cells to offer clinically relevant diagnostic information about cardiovascular disease. Ultraselective nanoparticle targeting of Ly-6C^hi monocytes and foamy macrophages and clinically-viable photoacoustic imaging (PAI) are combined in order to precisely and specifically image inflamed plaques ex vivo in a mouse model that mimics human vulnerable plaques histopathologically. Within the plaques, high-dimensional single-cell flow cytometry (13-parameter) shows that the nanoparticles are almost-exclusively taken up by the Ly-6C^hi monocytes and foamy macrophages that heavily infiltrate plaques. PAI identifies inflamed atherosclerotic plaques that display ≈6-fold greater signal compared to controls (P < 0.001) 6 h after intravenous injection of ultraselective carbon nanotubes, with in vivo corroboration via optical imaging. This highly-selective strategy may provide a targeted, noninvasive imaging strategy to accurately identify and diagnose inflamed atherosclerotic lesions.