Photo-metallo-immunotherapy: Fabricating Chromium-Based Nanocomposites to Enhance CAR-T Cell Infiltration and Cytotoxicity against Solid Tumors.

The infiltration and cytotoxicity of chimeric antigen receptor (CAR)-T cells are crucial for effective elimination of solid tumors. While metallo-immunotherapy is a promising strategy that can activate the antitumor immunity, its role in promoting CAR-T cell therapy remains elusive. The first single-element nanomaterial based on chromium nanoparticles (Cr NPs) for cancer photo-metallo-immunotherapy has been reported previously. Herein, an extended study using biodegradable polydopamine as a versatile carrier for these nanoparticles, enabling synergistic CAR-T cell therapy, is reported. The results show that these nanocomposites with or without further encapsulation of the anticancer drug alpelisib can promote the CAR-T cell migration and antitumor effect. Upon irradiation with near-infrared light, they caused mild hyperthermia that can "warm" the "cold" tumor microenvironment (TME). The administration of B7-H3 CAR-T cells to NOD severe combined immunodeficiency gamma mice bearing a human hepatoma or PIK3CA-mutated breast tumor can significantly inhibit the tumor growth after the induction of tumor hyperthermia by the nanocomposites and promote the secretion of serum cytokines, including IL-2, IFN-γ, and TNF-α. The trivalent Cr3+ ions, which are the major degradation product of these nanocomposites, can increase the CXCL13 and CCL3 chemokine expressions to generate tertiary lymphoid structures (TLSs) in the tumor tissues, facilitating the CAR-T cell infiltration.

Effect of Chromium Nanoparticles and Switching from a High-Fat to a Low-Fat Diet on the Cecal Microenvironment in Obese Rats.

Previous studies showed that chromium nanoparticles (Cr-NPs) might be used as dietary compounds against some obesity-related disorders; however, there is little information on how these compounds influence the gut microenvironment. The aim of this study was to investigate whether the negative effects of a high-fat diet in the large intestine of rats might be mitigated by switching to a low-fat diet and supplementation with Cr-NPs. Microbiota sequencing analysis revealed that the main action of the Cr-NPs was focused on changing the gut microbiota's activity. Supplementation with nanoparticles decreased the activity of ß-glucuronidase and enzymes responsible for the hydrolysis of dietary oligosaccharides and, thus, lowered the concentration of short-chain fatty acids in the cecum. In this group, there was also an elevated level of cecal lithocholic acid. The most favorable effect on the regulation of obesity-related disorders was observed when a high-fat diet was switched to a low-fat diet. This dietary change enhanced the production of short-chain fatty acids, reduced the level of secondary bile acids, and increased the microbial taxonomic richness, microbial differences, and microbial enzymatic activity in the cecum. To conclude, supplementation of a high-fat diet with Cr-NPs primarily had an effect on intestinal microbial activity, but switching to a low-fat diet had a powerful, all-encompassing effect on the gut that improved both microbial activity and composition.

Sequential-Dependent Synthesis of Bimetallic Silver-Chromium Nanoparticles for Multichannel Sensing, Logic Computing, and 3 in 1 Information Protection.

Bimetallic nanomaterials (BNMs) have been used in sensing, biomedicine, and environmental remediation, but their multipurpose and comprehensive applications in molecular logic computing and information security protection have received little attention. Herein, This synthesis method is achieved by sequentially adding reactants under ice bath conditions. Interestingly, Ag-Cr NPs can dynamically selectively sense anions and reductants in multiple channels. Especially, ClO- can be quantitatively detected by oxidizing Ag-Cr NPs with detection limits of 98.37 nM (at 270 nm) and 31.83 nM (at 394 nm). Based on sequential-dependent synthesis process of Ag-Cr NPs, Boolean logic gates and customizable molecular keypad locks are constructed by setting the reactants as the inputs, the states of the resulting solutions as the outputs. Furthermore, dynamically selective response patterns of the Ag-Cr NPs can be converted into binary strings to exploit molecular crypto-steganography to encode, store, and hide information. By integrating the three dimensions of authorization, encryption, and steganography, 3 in 1 advanced information protection based on Ag-Cr nanosensing system can be achieved, which can enhance the anti-cracking ability of information. This research will promote the development and application of nanocomposites in the field of information security and deepen the connection between molecular sensing and the information world.

Effects of Different Chromium Compounds on Hematology and Inflammatory Cytokines in Rats Fed High-Fat Diet.

The aim of the study was to determine how a high-fat diet supplemented with various forms of chromium affects hematological and immune parameters of the blood of rats. The rats received a standard diet or a high-fat diet supplemented with chromium at 0.3 mg/kg body weight (BW) in the form of chromium(III) picolinate, chromium(III)-methionine or nano-sized chromium. Selected hematological parameters were determined in the blood of the rats, including total white blood cell (WBC) count, leukogram, red blood cell (RBC) count, hemoglobin level (HGB), hematocrit (HCT), platelet count (PLT) and platelet percentage (PCT), as well as immune parameters: levels of immunoglobulins A and E (IgA and IgE), interleukin-6 (IL-6), interleukin-2 (IL-2), and tumor necrosis factor α (TNF-α); activity of ceruloplasmin (Cp); and levels of caspase 3 and 8 (Casp3 and Casp8). Feeding rats a high-fat diet increased blood markers of induction of inflammation, ie pro-inflammatory cytokines IL-6 and TNF-α, and also significantly increased IgE. The diet had no effect on the blood count, except for an increase in the number of neutrophils. The chromium compounds tested, particularly Cr-Met and Cr-NPs, stimulated the immune system of the rats, as indicated by increased concentrations of IgA, IgE, IL-2, IL-6, TNF-α, and Cp. Given the increase in inflammatory mediators induced by chromium, it should not be used to mitigate the effects of a high-fat diet. Moreover, chromium picolinate and chromium nanoparticles were shown to increase the content of caspase 3 and 8 in the blood of rats, which indicates a pro-apoptotic effect. The effects of the use of chromium nanoparticles include reductions in the WBC count and in the thrombocyte count (leuko- and thrombopenia). Taking account these data the use of chromium as dietary supplement should be reconsidered.

Novel Green Biosynthesis of 5-Fluorouracil Chromium Nanoparticles Using Harpullia pendula Extract for Treatment of Colorectal Cancer.

Colorectal cancer (CRC) is the third highest major cause of morbidity and mortality worldwide. Hence, many strategies and approaches have been widely developed for cancer treatment. This work prepared and evaluated the antitumor activity of 5-Fluorouracil (5-Fu) loaded chromium nanoparticles (5-FuCrNPs). The green biosynthesis approach using Harpullia (H) pendula aqueous extract was used for CrNPs preparation, which was further loaded with 5-Fu. The prepared NPs were characterized for morphology using scanning and transmission electron microscopes (SEM and TEM). The results revealed the formation of uniform, mono-dispersive, and highly stable CrNPs with a mean size of 23 nm. Encapsulation of 5-Fu over CrNPs, with a higher drug loading efficiency, was successful with a mean size of 29 nm being produced. In addition, Fourier transform infrared (FTIR) and X-ray diffraction pattern (XRD) were also used for the investigation. The drug 5-Fu was adsorbed on the surface of biosynthesized CrNPs in order to overcome its clinical resistance and increase its activity against CRC cells. Box-Behnken Design (BBD) and response surface methodology (RSM) were used to characterize and optimize the formulation factors (5-Fu concentration, CrNP weight, and temperature). Furthermore, the antitumor activity of the prepared 5-FuCrNPs was tested against CRC cells (CACO-2). This in vitro antitumor study demonstrated that 5-Fu-loaded CrNPs markedly decreased the IC50 of 5-Fu and exerted more cytotoxicity at nearly all concentrations than 5-Fu alone. In conclusion, 5-FuCrNPs is a promising drug delivery system for the effective treatment of CRC.

Assessment of DNA Methylation and Oxidative Changes in the Heart and Brain of Rats Receiving a High-Fat Diet Supplemented with Various Forms of Chromium.

The aim of the study was to determine how feeding rats a high-fat diet supplemented with various forms of chromium affects DNA methylation and oxidation reactions as well as the histology of heart and brain tissue. The rats received standard diet or high-fat diet and chromium at 0.3 mg/kg body weight (BW) in form of chromium (III) picolinate, chromium (III)-methionine, or nano-sized chromium. The content of malondialdehyde (MDA), protein carbonyl (PC), and 8-hydroxydeoxyguanosine (8-OHDG), the level of global DNA methylation and the activity of selected DNA repair enzymes were determined in the blood. In the brain and heart, the content of MDA, PC, 8-OHDG, and levels of global DNA methylation were determined. The brain was subjected to histological examination. The use of a high-fat diet was found to intensify epigenetic changes and oxidation reactions in the heart and brain. It was concluded that epigenetic changes and oxidation of lipids, proteins, and DNA in the heart and brain of rats resulting from the use of a high-fat diet cannot be limited by supplementing the diet with chromium. It was established that the use of chromium to supplement a high-fat diet intensifies the negative epigenetic and oxidative changes in the heart and brain, especially in the case of chromium nanoparticles.

Synthesis of antibacterial poly(o-chloroaniline)/chromium hybrid composites with enhanced electrical conductivity.

Electrically conductive polyorthochloroaniline/chromium nanocomposites (POC/Cr NCs) were prepared by in situ chemical oxidative polymerization of orthochloroaniline in the presence of Cr nanoparticles (Cr NPs). The load percentage of Cr nanofiller was varied in POC matrix to investigate the effect of Cr nanoparticles on the properties of the nanocomposites. The composition, structure, and morphology of POC and its composites were examined by Scanning electron microscopy, Fourier transform infrared spectroscopy, and UV-visible spectroscopic analysis. The antibacterial potential of POC and its composites was evaluated by the disc diffusion method against Escherichia coli and Bacillus subtilis. The results showed the improved antibacterial potential with the increase in the load percentage of nanofiller. The electrical conductivity of polymer and its composites was measured and correlated with the load percentage. The results showed that electrical conductivity of the composites was enhanced with the increase in load percentage of Cr nanoparticles.

Robust Ferromagnetism of Chromium Nanoparticles Formed in Superfluid Helium.

Chromium nanoparticles are formed using superfluid helium droplets as the nanoreactors, which are strongly ferromagnetic. The transition from antiferromagentism to ferromagnetism is attributed to atomic-scale disorder in chromium nanoparticles, leading to abundant unbalanced surface spins. Theoretical modeling confirms a frustrated aggregation process in superfluid helium due to the antiferromagnetic nature of chromium.

Fabrication of Size-Tunable Metallic Nanoparticles Using Plasmid DNA as a Biomolecular Reactor.

Plasmid DNA can be used as a template to yield gold, palladium, silver, and chromium nanoparticles of different sizes based on variations in incubation time at 70 °C with gold phosphine complexes, with the acetates of silver or palladium, or chromium acetylacetonate. The employment of mild synthetic conditions, minimal procedural steps, and aqueous solvents makes this method environmentally greener and ensures general feasibility. The use of plasmids exploits the capabilities of the biotechnology industry as a source of nanoreactor materials.