Fabrication of direct Z-scheme Cu2O@V-CN (octa) heterojunction with exposed (111) lattice planes and nitrogen-rich vacancies for rapid sterilization.

The Z-scheme heterojunction has demonstrated significant potential for promoting photogenerated carrier separation. However, the rational design of all-solid Z-scheme heterojunctions catalysts and the controversies about carrier transfer path of direct Z-scheme heterojunctions catalysts face various challenges. Herein, a novel heterojunction, Cu2O@V-CN (octa), was fabricated using V-CN (carbon nitride with nitrogen-rich vacancies) in-situ electrostatic self-wrapping Cu2O octahedra. Density functional theory (DFT) calculations revealed that the separation of carriers across the Cu2O@V-CN (octa) heterointerface was directly mapped to the Z-scheme mechanism compared to Cu2O/V-CN (sphere). This is because the Cu2O octahedra expose more highly active (111) lattice planes with more terminal Cu atoms and V-CN with abundant nitrogen vacancies to form delocalized electronic structures like electronic reservoirs. This facilitates the wrapping of Cu2O octahedra by V-CN and protects their stability via tighter interfacial contact, thus enhancing the tunneling of carriers for rapid photocatalytic sterilization. These findings provide novel approaches for designing high-efficiency Cu2O-based photocatalytic antifoulants for practical applications.

Full solar spectrum-driven Cu2O/PDINH heterostructure with enhanced photocatalytic antibacterial activity and mechanism insight.

Marine biofouling hazards the sustainable development of the environment and has become a potential threat to environmental and ecological security. Photocatalytic antibacterial agents driven by the full solar spectrum are promising antifouling agents for environmental protection. The cuprous oxide/perylene-3,4,9,10-tetracarboximide (Cu2O/PDINH) heterostructure was successfully constructed by integrating p-type Cu2O and n-type PDINH to improve photocatalytic antibacterial efficiency. PDINH extended the absorption spectrum from ultraviolet to near-infrared, improving light utilization by 75 %. The Cu2O/PDINH heterostructure reduced the toxicity risk of Cu2O for environmental pollution, achieved full solar spectrum drive and overcame the inherent defect that Cu2O cannot produce singlet oxygen. The Cu2O/PDINH heterostructure exhibited excellent long-term and photocatalytic antibacterial activity with an antibacterial rate of > 90 % due to the sterilization of copper ions and the continuous generation of ROS driven by the full solar spectrum. This inorganic-organic Cu2O/PDINH heterostructure shows great application prospects in energy and the environment. The Cu2O/PDINH heterostructure with effective ROS increase and superior photocatalytic sterilization efficiency has great potential for environmentally friendly marine antifouling agents.

Strategy for reducing the carriers transfer antagonistic effect between heterojunction and plasmonic effect and weakening photocorrosion of Cu2O for excellent photocatalytic bacteriostasis.

Heterogeneous catalysis composed of plasmonic metal and semiconductor has been utilized to tune local surface electron density in MOA (Molecular oxygen activation). However, there is a severe antagonistic effect between Schottky junction carriers and SPR (Surface Plasmon Resonance) induced hot carriers transfer routers when metal and semiconductor are both excited to dramatically reduce carriers separation efficiency. Hence, a highly effective photocatalytic antifoulant obtained by V-CN (carbon nitride with nitrogen vacancies) in-situ loading Cu2O and Ag nanoparticles (Cu2O/Ag/V-CN) was introduced to promote MOA to assist the metal ions sterilization. The DFT calculations (Density Functional Theory) and FEM calculations (Finite Element Method) intuitively proved the photocatalytic antifoulant belonged to a ternary Z-scheme heterojunction and could visibly weaken the antagonistic effect of hot carriers and Schottky carriers transport routes. The delocalized electron structure caused by V-CN and the effective electron mediator of Ag were the key to the formation of Z-scheme interfacial heterojunctions. These conclusions were also supported by experimental data, like more ∙O2- production capacity, efficient carriers separation, and higher carriers lifetime (27% higher than Cu2O and Cu2O/V-CN) as well as the weakened Cu2O photocorrosion tendency (Cu2O turning into CuO). Additionally, except for increasing nearly-three times adsorption energy of O2 for rapid activation, Cu2O/Ag/V-CN with abundant nitrogen vacancies can more significantly slow metal ions release (less about 97% to pure Cu2O and at least 22% higher than reported systems), which can observably save the amount of catalyst and heavy metals content. Therefore, Cu2O/Ag/V-CN has great potential for practical antifouling applications.

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

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.

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.

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.