Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation of very long-chain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. In contrast, these enzymes are silenced by DNA methylation in intestinal-type GCs, rendering cells resistant to ferroptosis. Lipid profiling and isotope tracing analyses revealed that intestinal-type GCs are unable to generate arachidonic acid (AA) and adrenic acid (AdA) from linoleic acid. AA supplementation of intestinal-type GCs restores their sensitivity to ferroptosis. Based on these data, the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroptosis; thus, this pathway potentially represents a marker for predicting the efficacy of ferroptosis-mediated cancer therapy.
Nanoparticles have been investigated as drug carriers, because they provide a great opportunity due to their advantageous features: (i) various formulations using organic/inorganic materials, (ii) easy modification of targeting molecules, drugs or other molecules on them, (iii) effective delivery to target sites, resulting in high therapeutic efficacy and (iv) controlling drug release by external/internal stimuli. Because of these features, therapeutic efficacy can be improved and unwanted side effects can be reduced. Theranostic nanoparticles have been developed by incorporating imaging agents in drug carriers as all-in-one system, which makes it possible to diagnose and treat cancer by monitoring drug delivery behavior simultaneously. Recently, stimuli-responsive, activatable nanomaterials are being applied that are capable of producing chemical or physical changes by external stimuli. By using these nanoparticles, multiple tasks can be carried out simultaneously, e.g., early and accurate diagnosis, efficient cataloguing of patient groups of personalized therapy and real-time monitoring of disease progress. In this paper, we describe various types of nanoparticles for drug delivery systems, as well as theranostic systems.
We fabricated dextran-coated magnetic nanoclusters (Dex-MNCs) for targeted magnetic resonance (MR) imaging of inflammatory macrophages. Dex-MNCs were prepared through encapsulation of hydrophobic magnetic nanocrystals (MNCs) by pyrenyl dextran in order that MNCs could achieve increased colloidal stability in aqueous phase as well as strongly interact with macrophages. Dex-MNCs exhibited biocompatibility and sufficient targeting efficiency against macrophages with strengthened MR contrast effect from in vitro/in vivo studies. Considering these results, we confirmed that Dex-MNCs could accurately detect inflammatory macrophage via MR imaging.
Smart drug delivery systems that are triggered by environmental conditions have been developed to enhance cancer therapeutic efficacy while limiting unwanted effects. Because cancer exhibits abnormally high local acidities compared to normal tissues (pH 7.4) due to Warburg effects, pH-sensitive systems have been researched for effective cancer therapy. Chitosan-based intelligent theragnosis nanocomposites, N-naphthyl-O-dimethymaleoyl chitosan-based drug-loaded magnetic nanoparticles (NChitosan-DMNPs), were developed in this study. NChitosan-DMNPs are capable of pH-sensitive drug release with MR-guided images because doxorubicin (DOX) and magnetic nanocrystals (MNCs) are encapsulated into the designed N-naphthyl-O-dimethymaleoyl chitosan (N-nap-O-MalCS). This system exhibits rapid DOX release as acidity increases, high stability under high pH conditions, and sufficient capacity for diagnosing and monitoring therapeutic responses. These results demonstrate that NChitosan-DMNPs have potential as theragnosis nanocomposites for effective cancer therapy.
Microporous carbon compartments (MCCs) were developed via controlled carbonization of wheat flour producing large cavities that allow CO2 gas molecules to access micropores and adsorb effectively. KOH activation of MCCs was conducted at 700 °C with varying mass ratios of KOH/C ranging from 1 to 5, and the effects of activation conditions on the prepared carbon materials in terms of the characteristics and behavior of CO2 adsorption were investigated. Textural properties, such as specific surface area and total pore volume, linearly increased with the KOH/C ratio, attributed to the development of pores and enlargement of pores within carbon. The highest CO2 adsorption capacities of 5.70 mol kg−1 at 0 °C and 3.48 mol kg−1 at 25 °C were obtained for MCC activated with a KOH/C ratio of 3 (MCC-K3). In addition, CO2 adsorption uptake was significantly dependent on the volume of narrow micropores with a pore size of less than 0.8 nm rather than the volume of larger pores or surface area. MCC-K3 also exhibited excellent cyclic stability, facile regeneration, and rapid adsorption kinetics. As compared to the pseudo-first-order model, the pseudo-second-order kinetic model described the experimental adsorption data methodically.
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