Biocompatible graphene-zirconia nanocomposite as a cyto-safe immunosensor for the rapid detection of carcinoembryonic antigen.

Graphene-based materials have gained remarkable attention in numerous disciplines owing to their unique electrochemical properties. Out of various hybridized nanocomposites, graphene-zirconia nanocomposite (GZ) was distinctive due to its biocompatibility. Zirconia nanoparticles serve as spacers that reduce the stacking of graphene and improve the electrochemical performance of the material. Considering that lungs and skin suffer the greatest exposure to nanoparticles, this study aimed to evaluate the cytotoxicity of the as-synthesized GZ nanocomposites on MRC5 (lung cells) and HaCaT (skin cells) via morphological observation and cell viability assay using 3-(4,5 dimethylthiazol-2-yl)-(2,5-diphenyltetrazolium bromide) tetrazolium (MTT). GZ-treated cells showed a comparable proliferation rate and morphology with untreated cells under microscopic evaluation. Based on MTT results, the IC50 values of GZ were > 500 µg/ml for MRC5 and HaCaT cells. The excellent biocompatibility was the supremacy of GZ over other nanocomposites applied as electrode materials in biosensors. GZ was functionalized with biolinker for the detection of carcinoembryonic antigen (CEA). The proposed immunosensor exhibited good responses towards CEA detection, with a 4.25 pg/ml LOD and correlation coefficient of R2 = 0.99 within a linear working range from 0.01 to 10 ng/ml. The performance of the immunosensor to detect CEA present in human serum was also evaluated. Good recovery of CEA was found, suggesting that the proposed immunosensor possess a high affinity to CEA even in a complex biological matrix, rendering it a promising sensing platform for real sample analysis and open a new way for the detection of cancer-associated proteins.

Parallel genome-wide RNAi screens identify lymphocyte-specific protein tyrosine kinase (LCK) as a targetable vulnerability of cell proliferation and chemoresistance in nasopharyngeal carcinoma.

Despite recent in advances in the management of nasopharyngeal carcinoma (NPC), development of targeted therapy remains challenging particularly in patients with recurrent or metastatic disease. To search for clinically relevant targets for the treatment of NPC, we carried out parallel genome-wide functional screens to identified essential genes that are required for NPC cells proliferation and cisplatin resistance. We identified lymphocyte-specific protein tyrosine kinase (LCK) as a key vulnerability of both proliferation and cisplatin resistance. Depletion of endogenous LCK or treatment of cells with LCK inhibitor induced tumor-specific cell death and synergized cisplatin sensitivity in EBV-positive C666-1 and EBV-negative SUNE1 cells. Further analyses demonstrated that LCK is regulating the proliferation and cisplatin resistance through activation of signal transducer and activator of transcription 5 (STAT5). Taken together, our study provides a molecular basis for targeting LCK and STAT5 signaling as potential druggable targets for the management of NPC.

Tocotrienols Modulate a Life or Death Decision in Cancers.

Malignancy often arises from sophisticated defects in the intricate molecular mechanisms of cells, rendering a complicated molecular ground to effectively target cancers. Resistance toward cell death and enhancement of cell survival are the common adaptations in cancer due to its infinite proliferative capacity. Existing cancer treatment strategies that target a single molecular pathway or cancer hallmark fail to fully resolve the problem. Hence, multitargeted anticancer agents that can concurrently target cell death and survival pathways are seen as a promising alternative to treat cancer. Tocotrienols, a minor constituent of the vitamin E family that have previously been reported to induce various cell death mechanisms and target several key survival pathways, could be an effective anticancer agent. This review puts forward the potential application of tocotrienols as an anticancer treatment from a perspective of influencing the life or death decision of cancer cells. The cell death mechanisms elicited by tocotrienols, particularly apoptosis and autophagy, are highlighted. The influences of several cell survival signaling pathways in shaping cancer cell death, particularly NF-κB, PI3K/Akt, MAPK, and Wnt, are also reviewed. This review may stimulate further mechanistic researches and foster clinical applications of tocotrienols via rational drug designs.

One-step green hydrothermal synthesis of biocompatible graphene/TiO2 nanocomposites for non-enzymatic H2O2 detection and their cytotoxicity effects on human keratinocyte and lung fibroblast cells.

Highly sensitive and selective immunosensors that can detect disease biomarkers at ultra-low levels in early stages are urgently needed to reduce mortality risks. A facile and efficient approach using sonochemical-assisted solvent graphene exfoliation and a hydrothermal synthesis method has been used to prepare graphene/titanium dioxide (G/TiO2) nanocomposites. Nanocomposites containing different ratios of graphene and TiO2 precursors were prepared to determine the optimum composition of G/TiO2 that has the highest conductivity and electrocatalytic properties. Characterisation methods such as X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), and high resolution TEM (HRTEM) were used to study the crystallinity, surface characteristics, elemental composition, and morphology of the synthesised nanocomposites. The synthesised materials were also confirmed via Raman spectroscopy. Using ferricyanide as the redox active probe, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) analyses indicated that 1 : 8 ratio of G/TiO2 exhibited the best current response and the lowest charge transfer resistance (Rct) of 1525 Ω. The potential of G/TiO2 for electrochemical sensing application was investigated using hydrogen peroxide (H2O2), a by-product of most enzymatic processes, as the analyte of interest. The sensitivity of the sensor towards H2O2 was 0.557 µA mM-1, with a limit of detection (LOD) at 56.89 µM. An in vitro cell proliferation assay was carried out to investigate the biocompatibility of the nanocomposites. The half-maximal inhibitory concentration (IC50) values obtained were >500 µg ml-1 for human lung fibroblasts (MRC5) and 5-25 µg ml-1 for human skin cells (HaCat).