A simultaneously GSH-depleted bimetallic Cu(ii) complex for enhanced chemodynamic cancer therapy.

A bimetallic Cu(ii) complex as a novel antitumor chemodynamic therapy agent with glutathione (GSH) depletion properties is successfully synthesized and well characterized. In tumor cells, the Cu2+ ions of the complex are reduced to Cu+ ions by GSH and then catalyzed by the overexpressed H2O2 to generate highly cytotoxic hydroxyl radicals (˙OH) that kill cancer cells. The complex is quickly taken up by cancer cells and distributed in multiple organelles including mitochondria and the nucleus. The complex demonstrates good cytotoxicity toward various cancer cell lines. However, its toxicity toward normal cells is significantly lower than that toward cancer cells due to the limited expression of H2O2. In addition, the complex could arrest the cell cycle of the G0/G1 phase, thereby inducing apoptosis rather than necrosis.

Maslinic acid protects against obesity-induced nonalcoholic fatty liver disease in mice through regulation of the Sirt1/AMPK signaling pathway.

Maslinic acid is a pentacyclic triterpenoid that is distributed in the peel of olives. Previous studies found that maslinic acid inhibited inflammatory response and antioxidant effects. We investigated whether maslinic acid ameliorates nonalcoholic fatty liver disease in mice with high-fat-diet (HFD)-induced obesity and evaluated the regulation of lipogenesis in hepatocytes. Male C57BL/6 mice fed a normal diet or HFD (60% fat, w/w) were tested for 16 wk. After the fourth week, mice were injected intraperitoneally with maslinic acid for 12 wk. In another experiment, HepG2 cells were treated with oleic acid to induce lipid accumulation or maslinic acid to evaluate lipogenesis. Maslinic acid significantly reduced body weight compared with HFD-fed mice. Maslinic acid reduced liver weight and liver lipid accumulation and improved hepatocyte steatosis. Furthermore, serum glucose, leptin, and free fatty acid concentrations significantly reduced, but the serum adiponectin concentration was higher, in the maslinic acid group than in the HFD group. In liver tissue, maslinic acid suppressed transcription factors involved in lipogenesis and increased adipose triglyceride lipase. In vitro, maslinic acid decreased lipogenesis by activating AMPK. These findings suggest that maslinic acid acts against hepatic steatosis by regulating enzyme activity involved in lipogenesis, lipolysis, and fatty acid oxidation in the liver.-Liou, C.-J., Dai, Y.-W., Wang, C.-L., Fang, L.-W., Huang, W.-C. Maslinic acid protects against obesity-induced nonalcoholic fatty liver disease in mice through regulation of the Sirt1/AMPK signaling pathway.

Ultrathin MoS2 nanosheets for high-performance photoelectrochemical applications via plasmonic coupling with Au nanocrystals.

In this work, we prepared ultrathin MoS2 nanosheets with exposed active edge sites and high electric conductivity that can sufficiently absorb light in the visible region to enable solar energy conversion. The gold nanocrystal-decorated MoS2 nanosheets facilitate sufficiently enhanced photoelectrochemical water splitting in the UV-visible region. Different Au nanostructures, such as Au nanoparticles and nanorods, were modified on the surface of MoS2 nanosheets to promote photoelectrochemical water decomposition. By spin-coating a synthetic gold-modified MoS2 hybrid photoanode on a FTO substrate, the efficiency of photoelectrochemical water oxidation was significantly enhanced, by 2 times (nanorods) and 3.5 times (nanoparticles) in the visible-infrared region; furthermore, the average optical resistance was reduced by a factor of two compared to the MoS2 photoanode without Au, and the photocurrent increases exponentially when the system bias was greater than 0.7 volts. The Au-MoS2 metal-semiconductor interface plays an important role in studying the surface plasmon interactions, charge transfer mechanism, and electric field amplification. This rational design for such a unique hybrid nanostructure explains the plasmon-enhanced photoelectrochemical water splitting. This current contribution provides a new path for using the plasmonic metal/semiconductor heterostructure to effectively harvest UV-visible light for solar fuel generation.

Au@SiO2@CuInS2-ZnS/Anti-AFP fluorescent probe improves HCC cell labeling.

BACKGROUND: Clear tumor imaging is essential to the resection of hepatocellular carcinoma (HCC). This study aimed to create a novel biological probe to improve the HCC imaging. METHODS: Au nano-flower particles and CuInS2-ZnS core-shell quantum dots were synthesized by hydrothermal method. Au was coated with porous SiO2 and combined with anti-AFP antibody. HCC cell line HepG2 was used to evaluate the targeting efficacy of the probe, while flow cytometry and MTT assay were used to detect the cytotoxicity and bio-compatibility of the probe. Probes were subcutaneously injected to nude mice to explore light intensity and tissue penetration. RESULTS: The fluorescence stability of the probe was maintained 100% for 24 h, and the brightness value was 4 times stronger than that of the corresponding CuInS2-ZnS quantum dot. In the targeting experiment, the labeled HepG2 emitted yellow fluorescence. In the cytotoxicity experiments, MTT and flow cytometry results showed that the bio-compatibility of the probe was fine, the inhibition rate of HepG2 cell with 60% Cu-QDs/Anti-AFP probe and Au-QDs/Anti-AFP probe solution for 48 h were significantly different (86.3%±7.0% vs. 4.9%±1.3%, t = 19.745, P<0.05), and the apoptosis rates were 83.3%±5.1% vs. 4.4%±0.8% (P<0.001). In the animal experiment, the luminescence of the novel probe can penetrate the abdominal tissues of a mouse, stronger than that of CuInS2-ZnS quantum dot. CONCLUSIONS: The Au@SiO2@CuInS2-ZnS/Anti-AFP probe can targetedly recognize and label HepG2 cells with good bio-compatibility and no toxicity, and the strong tissue penetrability of luminescence may be helpful to surgeons.

Polyelectrolyte-Mediated Nontoxic AgGa xIn1- xS2 QDs/Low-Density Lipoprotein Nanoprobe for Selective 3D Fluorescence Imaging of Cancer Stem Cells.

Cancer stem cells, which are a population of cancer cells sharing common properties with normal stem cells, have strong self-renewal ability and multi-lineage differentiation potential to trigger tumor proliferation, metastases, and recurrence. From this, targeted therapy for cancer stem cells may be one of the most promising strategies for comprehensive treatment of tumors in the future. We design a facile approach to establish the colon cancer stem cells-selective fluorescent probe based on the low-density lipoprotein (LDL) and the novel AgGa xIn(1- x)S2 quantum dots (AGIS QDs). The AGIS QDs with a high crystallinity are obtained for the first time via cation-exchange protocol of Ga3+ to In3+ starting from parent AgInS2 QDs. Photoluminescence peak of AGIS QDs can be turned from 502 to 719 nm by regulating the reaction conditions, with the highest quantum yield up to 37%. Subsequently, AGIS QDs-conjugated LDL nanocomposites (NCs) are fabricated, in which a cationic polyelectrolyte was used as a coupling reagent to guarantee the electrostatic self-assembly. The structural integrity and physicochemical properties of the LDL-QDs NCs are found to be maintained in vitro, and the NCs exhibit remarkable biocompatibility. The LDL-QDs can be selectively delivered into cancer stem cells that overexpress LDL receptor, and three-dimensional imaging of cancer stem cells is realized. The results of this study not only demonstrate the versatility of nature-derived lipoprotein nanoparticles, but also confirm the feasibility of electrostatic conjugation using cationic polyelectrolyte, allowing reseachers to design nanoarchitectures for targeted diagnosis and treatment of cancer.

Phloretin ameliorates chemokines and ICAM-1 expression via blocking of the NF-κB pathway in the TNF-α-induced HaCaT human keratinocytes.

Previous studies found that phloretin had anti-oxidant, anti-inflammatory, and anti-tumor properties. In this study, we investigated whether phloretin could suppress the production of the intercellular adhesion molecule (ICAM)-1 and chemokines through downregulation of the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in TNF-α-stimulated HaCaT human keratinocytes. HaCaT cells were treated with phloretin and then the cells were stimulated by TNF-α. Phloretin treatment decreased the production of IL-6, IL-8, CCL5, MDC, and TARC. Phloretin decreased ICAM-1 protein and mRNA expression, and also suppressed the adhesion of monocyte THP-1 cells to inflammatory HaCaT cells. Phloretin inhibited NF-κB translocation into the nucleus and also suppressed the phosphorylation of Akt and MAPK signal. In addition, phloretin increased heme oxygenase-1 production in a concentration-dependent manner. These results demonstrated that phloretin has anti-inflammatory effects to inhibit chemokines and ICAM-1 expressions through suppression of the NF-κB and MAPK pathways in human keratinocytes.