ZnO-Graphene Oxide Nanocomposite for Paclitaxel Delivery and Enhanced Toxicity in Breast Cancer Cells.

A ZnO-Graphene oxide nanocomposite (Z-G) was prepared in order to exploit the biomedical features of each component in a single anticancer material. This was achieved by means of an environmentally friendly synthesis, taking place at a low temperature and without the involvement of toxic reagents. The product was physicochemically characterized. The ZnO-to-GO ratio was determined through thermogravimetric analysis, while scanning electron microscopy and transmission electron microscopy were used to provide insight into the morphology of the nanocomposite. Using energy-dispersive X-ray spectroscopy, it was possible to confirm that the graphene flakes were homogeneously coated with ZnO. The crystallite size of the ZnO nanoparticles in the new composite was determined using X-ray powder diffraction. The capacity of Z-G to enhance the toxicity of the anticancer drug Paclitaxel towards breast cancer cells was assessed via a cell viability study, showing the remarkable anticancer activity of the obtained system. Such results support the potential use of Z-G as an anticancer agent in combination with a common chemotherapeutic like Paclitaxel, leading to new chemotherapeutic formulations.

Facile one-pot hydrothermal synthesis of a zinc oxide/curcumin nanocomposite with enhanced toxic activity against breast cancer cells.

Zinc oxide/Curcumin (Zn(CUR)O) nanocomposites were prepared via hydrothermal treatment of Zn(NO3)2 in the presence of hexamethylenetetramine as a stabilizing agent and CUR as a bioactive element. Three ZnO : CUR ratios were investigated, namely 57 : 43 (Zn(CUR)O-A), 60 : 40 (Zn(CUR)O-B) and 81 : 19 (Zn(CUR)O-C), as assessed by thermogravimetric analyses, with an average hydrodynamic diameter of nanoaggregates in the range of 223 to 361 nm. The interaction of CUR with ZnO via hydroxyl and ketoenol groups (as proved by X-ray photoelectron spectroscopy analyses) was found to significantly modify the key properties of ZnO nanoparticles with the obtainment of a bilobed shape (as shown by scanning electron microscopy), and influenced the growth process of the composite nanoparticles as indicated by the varying particle sizes determined by powder X-ray diffraction. The efficacy of Zn(CUR)O as anticancer agents was evaluated on MCF-7 and MDA-MB-231 cancer cells, obtaining a synergistic activity with a cell viability depending on the CUR amount within the nanocomposite. Finally, the determination of reactive oxygen species production in the presence of Zn(CUR)O was used as a preliminary evaluation of the mechanism of action of the nanocomposites.

The Impact of Nε-Acryloyllysine Piperazides on the Conformational Dynamics of Transglutaminase 2.

In addition to the classic functions of proteins, such as acting as a biocatalyst or binding partner, the conformational states of proteins and their remodeling upon stimulation need to be considered. A prominent example of a protein that undergoes comprehensive conformational remodeling is transglutaminase 2 (TGase 2), the distinct conformational states of which are closely related to particular functions. Its involvement in various pathophysiological processes, including fibrosis and cancer, motivates the development of theranostic agents, particularly based on inhibitors that are directed toward the transamidase activity. In this context, the ability of such inhibitors to control the conformational dynamics of TGase 2 emerges as an important parameter, and methods to assess this property are in great demand. Herein, we describe the application of the switchSENSE® principle to detect conformational changes caused by three irreversibly binding Nε-acryloyllysine piperazides, which are suitable radiotracer candidates of TGase 2. The switchSENSE® technique is based on DNA levers actuated by alternating electric fields. These levers are immobilized on gold electrodes with one end, and at the other end of the lever, the TGase 2 is covalently bound. A novel computational method is introduced for describing the resulting lever motion to quantify the extent of stimulated conformational TGase 2 changes. Moreover, as a complementary biophysical method, native polyacrylamide gel electrophoresis was performed under similar conditions to validate the results. Both methods prove the occurrence of an irreversible shift in the conformational equilibrium of TGase 2, caused by the binding of the three studied Nε-acryloyllysine piperazides.

Curcumin and Graphene Oxide Incorporated into Alginate Hydrogels as Versatile Devices for the Local Treatment of Squamous Cell Carcinoma.

With the aim of preparing hybrid hydrogels suitable for use as patches for the local treatment of squamous cell carcinoma (SCC)-affected areas, curcumin (CUR) was loaded onto graphene oxide (GO) nanosheets, which were then blended into an alginate hydrogel that was crosslinked by means of calcium ions. The homogeneous incorporation of GO within the polymer network, which was confirmed through morphological investigations, improved the stability of the hybrid system compared to blank hydrogels. The weight loss in the 100-170 °C temperature range was reduced from 30% to 20%, and the degradation of alginate chains shifted to higher temperatures. Moreover, GO enhanced the stability in water media by counteracting the de-crosslinking process of the polymer network. Cell viability assays showed that the loading of CUR (2.5% and 5% by weight) was able to reduce the intrinsic toxicity of GO towards healthy cells, while higher amounts were ineffective due to the antioxidant/prooxidant paradox. Interestingly, the CUR-loaded systems were found to possess a strong cytotoxic effect in SCC cancer cells, and the sustained CUR release (~50% after 96 h) allowed long-term anticancer efficiency to be hypothesized.

Insight into bio-metal interface formation in vacuo: interplay of S-layer protein with copper and iron.

The mechanisms of interaction between inorganic matter and biomolecules, as well as properties of resulting hybrids, are receiving growing interest due to the rapidly developing field of bionanotechnology. The majority of potential applications for metal-biohybrid structures require stability of these systems under vacuum conditions, where their chemistry is elusive, and may differ dramatically from the interaction between biomolecules and metal ions in vivo. Here we report for the first time a photoemission and X-ray absorption study of the formation of a hybrid metal-protein system, tracing step-by-step the chemical interactions between the protein and metals (Cu and Fe) in vacuo. Our experiments reveal stabilization of the enol form of peptide bonds as the result of protein-metal interactions for both metals. The resulting complex with copper appears to be rather stable. In contrast, the system with iron decomposes to form inorganic species like oxide, carbide, nitride, and cyanide.

Graphene oxide - gelatin nanohybrids as functional tools for enhanced Carboplatin activity in neuroblastoma cells.

PURPOSE: Preparation of Nanographene oxide (NGO) - Gelatin hybrids for efficient treatment of Neuroblastoma. METHODS: Nanohybrids were prepared via non-covalent interactions. Spectroscopic tools have been used to discriminate the chemical states of NGO prior and after gelatin coating, with UV visible spectroscopy revealing the maximum binding capacity of gelatin to NGO. Raman and X-ray photoelectron spectroscopy (XPS) demonstrated NGO and Gelatin_NGO nanohybrids through a new chemical environments produced after noncovalent interaction. Microscopic analyses, atomic force microscopy (AFM) and scanning electron microscopy (SEM) are used to estimate the thickness of samples and the lateral width in the nanoscale, respectively. RESULTS: The cell viability assay validated Gelatin_NGO nanohybrids as a useful nanocarrier for Carboplatin (CP) release and delivery, without obvious signs of toxicity. The nano-sized NGO (200 nm and 300 nm) did not enable CP to kill the cancer cells efficiently, whilst the CP loaded Gel_NGO 100 nm resulted in a synergistic activity through increasing the local concentration of CP inside the cancer cells. CONCLUSIONS: The nanohybrids provoked high stability and dispersibility in physiological media, as well as enhanced the anticancer activity of the chemotherapy agent Carboplatin (CP) in human neuroblastoma cells.

Real-time study of the modification of the peptide bond by atomic calcium.

Strong chemical interaction between bacterial surface protein layers and calcium atoms deposited in situ on top was revealed by means of photoemission spectroscopy. The interaction appears to mainly happen at the oxygen site of the peptide bonds and involves a large charge transfer from Ca 4s states into the peptide backbone. Chemical kinetics of this reaction was characterized using time-dependent valence band photoemission, and the reaction rate constant was determined.