Targeted regulation of autophagy using nanoparticles: New insight into cancer therapy

Normal cells depend on autophagy to maintain cellular homeostasis by recycling damaged organelles and misfolded proteins and degrading toxic agents. Similar to apoptosis, targeting autophagy has been under attention in cancer therapy. However, autophagy has both pro-survival and pro-death functions in tumors, and its targeting requires further elucidation. The current review focuses on using nanoparticles for targeting autophagy in cancer treatment. Nanocarriers can deliver autophagy regulators along with chemotherapeutic agents leading to intracellular accumulation in cancer cells and synergistic cancer therapy. Furthermore, genetic tools such as siRNA and shRNA can be used for targeting molecular components that regulate autophagy, such as the ATG12-ATG5-ATG16L1 complex. A number of nanostructures, such as gold and zinc oxide nanoparticles, can be used to enhance oxidative stress-mediated apoptosis and autophagy, reducing cancer progression. Further, using nanoparticles to modulate autophagy potentiates the anti-tumor effects of cisplatin and gefitinib during chemotherapy. Polymeric nanoparticles, lipid-based nanostructures and carbon-based nanomaterials are among other nanoparticles capable of regulating autophagy in cancer cells. Of note, various regulatory components of autophagy such as ATGs, Beclin-1 and LC3-II can be affected by nanomaterials. Based on the role of nanomaterial-induced autophagy as pro-survival or pro-death, further targeting can potentiate the fight against cancer cells. © 2021 Elsevier B.V

Bilayer Suspension Plasma-Sprayed Thermal Barrier Coatings with Enhanced Thermal Cyclic Lifetime : Experiments and Modeling

Suspension plasma spraying (SPS) has been shown as a promising process to produce porous columnar strain tolerant coatings for thermal barrier coatings (TBCs) in gas turbine engines. However, the highly porous structure is vulnerable to crack propagation, especially near the topcoat-bondcoat interface where high stresses are generated due to thermal cycling. A topcoat layer with high toughness near the topcoat-bondcoat interface could be beneficial to enhance thermal cyclic lifetime of SPS TBCs. In this work, a bilayer coating system consisting of first a dense layer near the topcoat-bondcoat interface followed by a porous columnar layer was fabricated by SPS using Yttria-stabilised zirconia suspension. The objective of this work was to investigate if the bilayer topcoat architecture could enhance the thermal cyclic lifetime of SPS TBCs through experiments and to understand the effect of the column gaps/vertical cracks and the dense layer on the generated stresses in the TBC during thermal cyclic loading through finite element modeling. The experimental results show that the bilayer TBC had significantly higher lifetime than the single-layer TBC. The modeling results show that the dense layer and vertical cracks are beneficial as they reduce the thermally induced stresses which thus increase the lifetime

Residual stresses in environmental and thermal barrier coatings on curved superalloy substrates: Experimental measurements and modelling

Residual stresses within thermal barrier coated (TBC) systems are predicted using finite element models and are compared against experimental measurements taken using Raman and photo-stimulated luminescence piezo-spectroscopic methods. Two types of specimens were considered: flat specimens without TBC, and aerofoil shaped specimens with TBC. Comparisons between model predictions and experimentally measured stresses and also the relationship between substrate curvature and residual stresses on subsequent spallation of the aerofoil specimen were made. For the flat specimen, predicted and measured residual stresses are of the same order of magnitude. Both studies have indicated that larger compressive residual stresses arise from higher substrate curvatures. The results improve the understanding of initiation and propagation of TBC cracks which occurs preferentially at locations with high substrate convex curvature