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Background: Stimuli-responsive drug delivery systems have been proven to be a promising strategy to enhance tumor localization, overcome multidrug resistance (MDR), and reduce the side effects of chemotherapy agents. Objectives: In this study, a temperature and redox dual stimuli-responsive system using mesoporous silica nanoparticles (MSNs) for targeted delivery of doxorubicin (DOX) was developed. Methods: Mesoporous silica nanoparticles were capped with poly(N-isopropylacrylamide) (PNIPAM), a thermo-sensitive polymer, with atom transfer radical polymerization (ATRP) method, via disulfide bonds (DOX-MSN-S-S-PNIPAM) to attain a controlled system that releases DOX under glutathione-rich (GSH-rich) environments and temperatures above PNIPAM’s lower critical solution temperature (LCST). Morphological and physicochemical properties of the nanoparticles were indicated using transmission electron microscopy (TEM), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and Brunauer-Emmett-Teller (BET). The drug release tests were performed at 25°C and 41°C in the absence and presence of the DTT, and the obtained results confirmed the synergic effect of temperature and reductive agent on a dual responsive release profile with a 73% cumulative release at 41°C and reductive environment during 240 min. Results: The average loaded drug content and encapsulation efficacy were reported as 42% and 29.5% at the drug: nanoparticle ratio of 1.5: 1. In vitro cytotoxicity assays on MCF-7 cell lines indicated significant viability decreased in cells exposed to DOX-MSN-S-S-PNIPAM compared to the free drug (DOX). Conclusions: Based on the results, DOX-MSN-S-S-PNIPAM has shown much more efficiency with stimuli-responsive properties in comparison to DOX on MCF-7 cancer cell lines.

The inhibition of AKR1B10 has been recognized as a potential therapeutic approach to the treatment of various types of cancers. A novel series of compounds with imino-2H-chromen and phenylimino-2H-chromen scaffolds were synthesized by Knoevenagel condensation reaction. The in vitro cytotoxic activity of synthesized compounds was evaluated against MOLT-4 and SK-OV-3 cells. Among the tested compounds, N-(3,4-dimethoxyphenyl)-2-(phenylimino)-2H-chromene-3-carboxamide (8g) demonstrated potent inhibitory activity against both examined cell lines. The results of the molecular docking study suggested that this compound is involved in critical hydrogen-bonding interactions with the Val301 and Lue302 of AKR1B10 catalytic site.

In the present study, a new method for fabricating ZrO2/AZ31 nanocomposite fillers of gas tungsten arc (GTA) welding was developed by applying accumulative roll bonding (ARB) to the magnesium sheets coated with ZrO2 nanoparticles. The purpose of ARB was to create a uniform dispersion of ZrO2 nanoparticles in the fillers and to form a good interfacial bonding between the magnesium matrix and ZrO2 nanoparticles. After welding, the effect of ZrO2 nanoparticles on the microstructure and mechanical properties of weld was evaluated. The test results showed that the yield strength of weld was greatly increased when using the nanocomposite fillers. The improvement in the yield strength was attributed to the grain refinement, coefficient of thermal expansion mismatch and Orowan strengthening mechanisms.