Yongji Yang

Synthesis of highly luminescent Mn:ZnSe/ZnS nanocrystals in aqueous media

High-quality water-dispersible Mn(2+)-doped ZnSe core/ZnS shell (Mn:ZnSe/ZnS) nanocrystals have been synthesized directly in aqueous media. Overcoating a high bandgap ZnS shell around the Mn:ZnSe cores can bring forward an efficient energy transfer from the ZnSe host nanocrystals to the dopant Mn. The quantum yields of the dopant Mn photoluminescence in the as-prepared water-soluble Mn:ZnSe/ZnS core/shell nanocrystals can be up to 35 +/- 5%. The optical features and structure of the obtained Mn:ZnSe/ZnS core/shell nanocrystals have been characterized by UV-vis, PL spectroscopy, TEM, XRD and ICP elementary analysis. The influences of various experimental variables, including the Mn concentration, the Se/Zn molar ratio as well as the kind and amount of capping ligand used in the core production and shell deposition process, on the luminescent properties of the obtained Mn:ZnSe/ZnS nanocrystals have been systematically investigated.

Cytotoxicity of silica nanoparticles on HaCaT cells

Despite the widespread use of silica nanoparticles (SiO2 NPs) in biological and medical fields, their adverse effects have not been clearly elucidated. In this study, spherical SiO2 NPs with a 50 nm diameter were used to study their interaction with HaCaT cells. SiO2 NPs were found to be readily internalized into HaCaT cells and localized in the cytoplasm, lysosomes and autophagosomes. Decreased cell viability and damaged cell membrane integrity showed the cytotoxicity of SiO2 NPs. Significant glutathione depletion and reactive oxygen species generation, which reduced the cellular antioxidant level, could be the major factor of cytotoxicity induced by SiO2 NPs. Copyright

Mitochondrial injury induced by nanosized titanium dioxide in A549 cells and rats.

The nanosized titanium dioxide (nano-TiO2) is an important nanoscale compound applied in many different fields because of its superior performance. Here, an anatase nano-TiO2 showed cytotoxicity in a dosage-dependent manner, which was in accordance with changes of A549 cell ultrastructure, A549 cell viability and intracellular ATP level. The lungs of rats treated with single intratracheal instillation of nano-TiO2 were injured, which was demonstrated by changes of alveolar epithelial cell ultrastructure, lung tissue pathology and lung tissue MDA level. The results of this study indicated that nano-TiO2 should be related to the generation of intracellular reactive oxygen species (ROS), which injured mitochondria and prevented the synthesis of ATP. The cells were approaching to apoptosis eventually. In macroscopic view, the lungs inevitably suffered.

In vitro cytotoxicity of gold nanorods in A549 cells

Gold nanoparticles, which have unique physicochemical characteristics, are being used for an increasingly wide range of applications in biomedical research. In this study, gold nanorods (width of 25 nm, length of 52 nm) were found to be internalized by A549 cells and were primarily localized in the lysosomes and membranous vesicles. The integrity of the membranes of A549 cells exposed to gold nanorods for 4h was damaged, as indicated by laser scanning confocal microscopy (LSCM). Increased lactate dehydrogenase (LDH) leakage and decreased cell viability further indicated the concentration-dependent cytotoxicity of the gold nanorods to the A549 cells. Reactive oxygen species (ROS) production was induced in the A549 cells by the gold nanorods, and this effect was positively correlated with the concentration of the gold nanorods. The results of this study indicated that exposure to gold nanorods caused dose-dependent cytotoxicity in A549 cells and that oxidative stress may be the main factor causing cytotoxicity.

Antagonism of EGFR and Notch limits resistance to EGFR inhibitors and radiation by decreasing tumor-initiating cell frequency

An anti-EGFR/Notch antibody limits acquired resistance to EGFR inhibitors and radiation by reducing tumor-initiating cell frequency. Two targets for a bigger punch The epidermal growth factor receptor (EGFR) is a common target of therapeutics for a variety of different tumors, but tumors eventually become resistant to these drugs. One route to resistance is an increase in the number of cancer stem cells driven by the Notch pathway. To overcome this type of resistance, Hu et al. created a customized antibody called CT16, which can recognize both EGFR and Notch, simultaneously inhibiting both pathways. The authors tested this antibody in mouse models of non–small cell lung cancer, showing that it inhibits cancer stem cells and is more effective than antibodies against the individual pathways alone and in combination, particularly in the presence of radiation treatment. Epidermal growth factor receptor (EGFR) blockade and radiation are efficacious in the treatment of cancer, but resistance is commonly reported. Studies have suggested that dysregulation of Notch signaling and enrichment of the cancer stem cell population underlie these treatment challenges. Our data show that dual targeting of EGFR and Notch2/3 receptors with antibody CT16 not only inhibited signaling mediated by these receptors but also showed a strong anti–stem cell effect both in vitro and in vivo. Treatment with CT16 prevented acquired resistance to EGFR inhibitors and radiation in non–small cell lung cancer (NSCLC) cell line models and patient-derived xenograft tumors. CT16 also had a superior radiosensitizing impact compared with EGFR inhibitors. CT16 in combination with radiation had a larger antitumor effect than the combination of radiation with EGFR inhibitors or tarextumab. Mechanistically, CT16 treatment inhibits the stem cell–like subpopulation, which has a high mesenchymal gene expression and DNA repair activity, and reduces tumor-initiating cell frequency. This finding highlights the capacity of a combined blockade of EGFR and Notch signaling to augment the response to radiation and suggests that CT16 may achieve clinical efficacy when combined with radiation in NSCLC treatment.

Distribution of Graphene Oxide and TiO2-Graphene Oxide Composite in A549 Cells

Graphene and its derivatives are increasingly applied in nanoelectronics, biosensing, drug delivery, and biomedical applications. However, the information about its cytotoxicity remains limited. Herein, the distribution and cytotoxicity of graphene oxide (GO) and TiO2-graphene oxide composite (TiO2-GO composite) were evaluated in A549 cells. Cell viability and cell ultrastructure were measured. Our results indicated that GO could enter A549 cells and located in the cytoplasm and nucleus without causing any cell damage. TiO2 nanoparticles and GO would be separated after TiO2-GO composite entered A549 cells. TiO2-GO composite could induce cytotoxicity similar to TiO2 nanoparticles, which was probably attributed to oxidative stress. These results should be considered in the development of biological applications of GO and TiO2-GO composite.

Noninjection facile synthesis of Gram-scale highly luminescent CdSe multipod nanocrystals.

Nearly all reported approaches for synthesis of high quality CdSe nanocrystals (NCs) involved two steps of preparation of Cd or Se stock solution in advance and then mixing the two reactants via hot-injection in high temperature. In this manuscript, Gram-scale CdSe multipod NCs were facilely synthesized in a noninjection route with the use of CdO and Se powder directly as reactants in paraffin reaction medium containing small amount of oleic acid and trioctylphosphine. The influence of various experimental variables, including reaction temperature, nature and amount of surfactants, Cd-to-Se ratio, and the nature of reactants, on the morphology of the obtained CdSe NCs have been systematically investigated. After deposition of ZnS shell around the CdSe multipod NCs, the PL QY of the obtained CdSe/ZnS can be up to 85%. The reported noninjection preparation approach can satisfy the requirement of industrial production bearing the advantage of low-cost, reproducible, and scalable. Furthermore, this facile noninjection strategy provides a versatile route to large-scale preparation of other semiconductor NCs with multipod or other morphologies.

Effects of fullerene C60 nanoparticles on A549 cells

Fullerene C60 nanoparticles (C60 NPs) have been widely applied in many fields due to their excellent physical and chemical properties. As production and applications of C60 NPs expand, public concern about the potential risk to human health has also risen. The toxicity of C60 NPs was evaluated by the CCK-8 assay using the cultured human epithelial cell line A549. Cellular uptake of the C60 NPs was observed by TEM imaging. In our findings, C60 NPs could readily enter A549 cells and showed no significant toxicity. Exposure of cultured A549 cells to C60 NPs led to an increase of intracellular reactive oxygen species (ROS) while glutathione reductase activity was probably activated to generate more GSH to maintain a cellular oxidation-reduction equilibrium. The A549 cells responded to the ROS increases through the inauguration of autophagic responses, aimed at restoring cellular health and equilibrium.

Broad RTK-targeted therapy overcomes molecular heterogeneity-driven resistance to cetuximab via vectored immunoprophylaxis in colorectal cancer

The human epidermal growth factor receptor (EGFR) targeting chimeric monoclonal antibody, cetuximab (Erbitux®), is a widely used drug in the treatment of metastatic colorectal cancer. However, the activation of the extensive crosstalk among the EGFR family receptors as well as other tyrosine kinase receptors (RTKs) impairs the efficacy of the drug by fueling acquired resistance. To identify the responsible potential activation pathway underlying cetuximab resistance and generate novel treatment strategies, cetuximab-resistant colorectal cancer cell lines were generated and validated and a functional RNAi screen targeting human RTKs was used to identify extensive receptor tyrosine kinase signaling networks established in resistant cancer cells. MET, Axl, and IGF-1R were identified as contributors to the acquired resistance to cetuximab. Targeting vectored immunoprophylaxis (VIPs) to different RTKs were generated and characterized. Different VIP approaches were evaluated in vivo with parental and cetuximab-resistance xenografts and the RTKs in resistant cancer xenografts were inhibited with VIPs via re-sensitization to cetuximab treatment. Combination of VIPs was more broadly efficacious, mechanistically, due to co-blocking the EGFR/Axl/MET signaling pathway, which was cross-activated in the resistant cell lines. Moreover, a VIP-based procedural treatment strategy not only eliminated the tumor but also afforded long-lasting protection from tumor recurrence and resistance. Overall, EGFR-related RTK pathway-network activation represents a novel mechanism underlying cetuximab resistance. A broad VIP combination strategy and VIP-based procedural treatment strategy may be a recommended addition to cetuximab-based targeted therapy. Our results establish a new principle to achieve combined RTK inhibition and reverse drug resistance using a VIP approach.

TRIM14 regulates cell proliferation and invasion in osteosarcoma via promotion of the AKT signaling pathway

Recent studies have shown that some members of the tripartite motif-containing protein (TRIM) family serve as important regulators of tumorigenesis. However, the biological role of TRIM14 in osteosarcoma remains to be established. In this study, we showed that TRIM14 is upregulated in human osteosarcoma specimens and cell lines, and correlated with osteosarcoma progression and shorter patient survival times. Functional studies demonstrated that overexpression of TRIM14 enhances osteosarcoma cell proliferation, clone formation, cell cycle procession, migration and invasion in vitro and promotes tumor growth in vivo, and conversely, its silencing has the opposite effects. Furthermore, TRIM14 overexpression induced activation of the AKT pathway. Inhibition of AKT expression reversed the TRIM14-mediated promotory effects on cell growth and mobility, in addition to TRIM14-induced epithelial-to-mesenchymal transition (EMT) and cyclin D1 upregulation. Our findings collectively suggest that TRIM14 functions as an oncogene by upregulating the AKT signaling pathway in osteosarcoma cells, supporting its potential utility as a therapeutic target for this disease.