Targeting c-Myc with decoy oligodeoxynucleotide-loaded polycationic nanoparticles inhibits cell growth and induces apoptosis in cancer stem-like cells (NTERA-2).

BACKGROUND: An increase in cancer stem cell (CSC) populations and their resistance to common treatments could be a result of c-Myc dysregulations in certain cancer cells. In the current study, we investigated anticancer effects of c-Myc decoy ODNs loaded-poly (methacrylic acid-co-diallyl dimethyl ammonium chloride) (PMA-DDA)-coated silica nanoparticles as carriers on cancer-like stem cells (NTERA-2). METHODS AND RESULTS: The physicochemical characteristics of the synthesized nanocomposites (SiO2@PMA-DDA-DEC) were analyzed using FT-IR, DLS, and SEM techniques. UV-Vis spectrophotometer was applied to analyze the release pattern of decoy ODNs from the nanocomposite. Furthermore, uptake, cell viability, apoptosis, and cell cycle assays were used to investigate the anticancer effects of nanocomposites loaded with c-Myc decoy ODNs on NTERA-2 cancer cells. The results of physicochemical analytics demonstrated that SiO2@PMA-DDA-DEC nanocomposites were successfully synthesized. The prepared nanocomposites were taken up by NTERA-2 cells with high efficiency, and could effectively inhibit cell growth and increase apoptosis rate in the treated cells compared to the control group. Moreover, SiO2@PMA-DDA nanocomposites loaded with c-Myc decoy ODNs induced cell cycle arrest at the G0/G1 phase in the treated cells. CONCLUSIONS: The conclusion drawn from this study is that c-Myc decoy ODN-loaded SiO2@PMA-DDA nanocomposites can effectively inhibit cell growth and induce apoptosis in NTERA-2 cancer cells. Moreover, given that a metal core is incorporated into this synthetic nanocomposite, it could potentially be used in conjunction with irradiation as part of a decoy-radiotherapy combinational therapy in future investigations.

Polydopamine contained hydrogel nanocomposites with combined antimicrobial and antioxidant properties for accelerated wound healing.

Overproduction of reactive oxygen species (ROS) in infected wounds induces a tremendous inflammatory reaction to delay wound healing. To address this problem, we designed a multifunctional polyacrylamide/PVA-based hydrogel containing synthesized poly(1-glycidyl-3-butylimidazolium salicylate) (polyGBImSal) and fabricated polydopamine-coated polyphenolic nanosheet (PDA@PNS) for wound dressing. The PDA@PNS particles were designed to induce I) antioxidant and anti-inflammatory features through ROS-scavenging and II) cell adhesive properties by the existing polydopamine into the hydrogels. The poly(ionic liquid)-based polyGBImSal was designed to allocate effective hydrogel antimicrobial activity. The fabricated hydrogel nanocomposites showed excellent properties in the swelling ratio, cell adhesiveness, protein adsorption, and anti-inflammatory, proving their general performance for application in wound healing. Furthermore, these hydrogels showed high antimicrobial activity (over 95 %) against three common wound-infecting pathogenic microbes: Escherichia coli, Staphylococcus aureus, and Candida albicans. The healing process of full-thickness dermal wounds in rats was accelerated by applying hydrogel nanocomposites with 0.5 wt% of PDA@PNS and 28 wt% of polyGBImSal. The wound closure contraction attained full closure, reaching 100 %, after 14 days, contrasted with the control group employing commercial wound dressing (Tegaderm), which achieved a closure rate of 68 % within the equivalent timeframe. These results make these hydrogel nanocomposites promising candidates for multifunctional wound dressing applications.

Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells.

In the present study, we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer cells. Myc decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics assays. ODNs were loaded on the synthesized Se@BSA@Chi-MTX nanostructure. The physicochemical characteristics of nanostructures were determined by FTIR, DLS, UV-vis, TEM, EDX, in vitro release, and hemolysis tests. Subsequently, the cytotoxicity properties of them with and without X-irradiation were investigated by uptake, MTT, cell cycle, apoptosis, and scratch assays on the LNCaP cell line. The results of DLS and TEM showed negative charge (-9 mV) and nanometer size (40 nm) for Se@BSA@Chi-DEC-MTX NPs, respectively. The results of FTIR, UV-vis, and EDX showed the proper interaction of different parts and the correct synthesis of nanoparticles. The results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/mL. The ODNs release from the nanostructures showed a pH-dependent manner, and the release rate was 15% higher in acidic pH. The targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen (PSMA). The significant synergistic effects of nanostructure (containing MTX drug) treatment along with X-irradiation showed cell growth inhibition, apoptosis induction (~57%), cell cycle arrest (G2/M phase), and migration inhibition (up to 90%) compared to the control. The results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP cells. This nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.

Developing techniques for cause-responsibility analysis of occupational accidents.

The aim of this study was to specify the causes of occupational accidents, determine social responsibility and the role of groups involved in work-related accidents. This study develops occupational accidents causes tree, occupational accidents responsibility tree, and occupational accidents component-responsibility analysis worksheet; based on these methods, it develops cause-responsibility analysis (CRA) techniques, and for testing them, analyzes 100 fatal/disabling occupational accidents in the construction setting that were randomly selected from all the work-related accidents in Tehran, Iran, over a 5-year period (2010-2014). The main result of this study involves two techniques for CRA: occupational accidents tree analysis (OATA) and occupational accidents components analysis (OACA), used in parallel for determination of responsible groups and responsibilities rate. From the results, we find that the management group of construction projects has 74.65% responsibility of work-related accidents. The developed techniques are purposeful for occupational accidents investigation/analysis, especially for the determination of detailed list of tasks, responsibilities, and their rates. Therefore, it is useful for preventing work-related accidents by focusing on the responsible group's duties.