Thikra Mustafa

Carbon Nanotubes as Plant Growth Regulators: Effects on Tomato Growth, Reproductive System, and Soil Microbial Community

Multi-walled carbon nanotubes (CNTs) can affect plant phenotype and the composition of soil microbiota. Tomato plants grown in soil supplemented with CNTs produce two times more flowers and fruit compared to plants grown in control soil. The effect of carbon nanotubes on microbial community of CNT-treated soil is determined by denaturing gradient gel electrophoresis and pyrosequencing analysis. Phylogenetic analysis indicates that Proteobacteria and Bacteroidetes are the most dominant groups in the microbial community of soil. The relative abundances of Bacteroidetes and Firmicutes are found to increase, whereas Proteobacteria and Verrucomicorbia decrease with increasing concentration of CNTs. The results of comparing diversity indices and species level phylotypes (OTUs) between samples showed that there is not a significant affect on bacterial diversity.

Mechanistic toxicity evaluation of uncoated and PEGylated single-walled carbon nanotubes in neuronal PC12 cells.

We investigated and compared the concentration-dependent cytotoxicity of single-walled carbon nanotubes (SWCNTs) and SWCNTs functionalized with polyethylene glycol (SWCNT-PEGs) in neuronal PC12 cells at the biochemical, cellular, and gene expressional levels. SWCNTs elicited cytotoxicity in a concentration-dependent manner, and SWCNT-PEGs exhibited less cytotoxic potency than uncoated SWCNTs. Reactive oxygen species (ROS) were generated in both a concentration- and surface coating-dependent manner after exposure to these nanomaterials, indicating different oxidative stress mechanisms. More specifically, gene expression analysis showed that the genes involved in oxidoreductases and antioxidant activity, nucleic acid or lipid metabolism, and mitochondria dysfunction were highly represented. Interestingly, alteration of the genes is also surface coating-dependent with a good correlation with the biochemical data. These findings suggest that surface functionalization of SWCNTs decreases ROS-mediated toxicological response in vitro.

Circulating tumor cell identification by functionalized silver-gold nanorods with multicolor, super-enhanced SERS and photothermal resonances

Nanotechnology has been extensively explored for cancer diagnostics. However, the specificity of current methods to identify simultaneously several cancer biomarkers is limited due to color overlapping of bio-conjugated nanoparticles. Here, we present a technique to increase both the molecular and spectral specificity of cancer diagnosis by using tunable silver-gold nanorods with narrow surface-enhanced Raman scattering (SERS) and high photothermal contrast. The silver-gold nanorods were functionalized with four Raman-active molecules and four antibodies specific to breast cancer markers and with leukocyte-specific CD45 marker. More than two orders of magnitude of SERS signal enhancement was observed from these hybrid nanosystems compared to conventional gold nanorods. Using an antibody rainbow cocktail, we demonstrated highly specific detection of single breast cancer cells in unprocessed human blood. By integrating multiplex targeting, multicolor coding, and multimodal detection, our approach has the potential to improve multispectral imaging of individual tumor cells in complex biological environments.

Photothermal nanodrugs: potential of TNF-gold nanospheres for cancer theranostics

Nanotechnology has been extensively explored for drug delivery. Here, we introduce the concept of a nanodrug based on synergy of photothermally-activated physical and biological effects in nanoparticle-drug conjugates. To prove this concept, we utilized tumor necrosis factor-alpha coated gold nanospheres (Au-TNF) heated by laser pulses. To enhance photothermal efficiency in near-infrared window of tissue transparency we explored slightly ellipsoidal nanoparticles, its clustering, and laser-induced nonlinear dynamic phenomena leading to amplification and spectral sharpening of photothermal and photoacoustic resonances red-shifted relatively to linear plasmonic resonances. Using a murine carcinoma model, we demonstrated higher therapy efficacy of Au-TNF conjugates compared to laser and Au-TNF alone or laser with TNF-free gold nanospheres. The photothermal activation of low toxicity Au-TNF conjugates, which are in phase II trials in humans, with a laser approved for medical applications opens new avenues in the development of clinically relevant nanodrugs with synergistic antitumor theranostic action.

Multifunctional Magnetic Nanoparticles for Synergistic Enhancement of Cancer Treatment by Combinatorial Radio Frequency Thermolysis and Drug Delivery

Few-layer, carbon-coated, iron (C/Fe) magnetic nanoparticles (MNPs) were synthesized with controlled sizes ranging from 7 to 9 nm. The additional loading of two anti-cancer drugs, doxorubicin and erlotinib, was achieved through - stacking onto the carbon shells. Controlled release of the drugs was successfully triggered by radio frequency (RF) heating or pH variation. Based on the experimental results, C/Fe MNPs act as heat-inducing agents and are able to thermally destroy cancer cells when RF is applied. It was found that the combination of anti-cancer drugs (in particular a low dose of doxorubicin) and RF treatment demonstrates a synergistic effect in inducing cell death in pancreatic cancer cells. Our findings demonstrate that MNPs can be used as highly efficient multimodal nanocarrier agents for an integrated approach to cancer treatment involving triggered delivery of antineoplastic drugs and RF-induced thermal therapy.

Ethylenediamine functionalized-single-walled nanotube (f-SWNT)-assisted in vitro delivery of the oncogene suppressor p53 gene to breast cancer MCF-7 cells

A gene delivery concept based on ethylenediamine-functionalized single-walled carbon nanotubes (f-SWCNTs) using the oncogene suppressor p53 gene as a model gene was successfully tested in vitro in MCF-7 breast cancer cells. The f-SWCNTs-p53 complexes were introduced into the cell medium at a concentration of 20 μg mL−1 and cells were exposed for 24, 48, and 72 hours. Standard ethidium bromide and acridine orange assays were used to detect apoptotic cells and indicated that a significantly larger percentage of the cells (approx 40%) were dead after 72 hours of exposure to f-SWCNTs-p53 as compared to the control cells, which were exposed to only p53 or f-SWCNTs, respectively. To further support the uptake and expression of the genes within the cells, green fluorescent protein-tagged p53, attached to the f-SWCNTs was added to the medium and the complex was observed to be strongly expressed in the cells. Moreover, caspase 3 activity was found to be highly enhanced in cells incubated with the f-SWCNTs-p53 complex, indicating strongly induced apoptosis. This system could be the foundation for novel gene delivery platforms based on the unique structural and morphological properties of multi-functional nanomaterials.

Structural and optoelectronic properties of P3HT-graphene composites prepared by in situ oxidative polymerization

Poly(3-hexylthiophene) (P3HT)-graphene nanocomposites were synthesized via in situ oxidative polymerization of 3-hexylthiophene monomer in the presence of graphene. The main thrust was to investigate the structural and optoelectronic properties of P3HT-graphene nanocomposites with various graphene concentrations. NMR spectroscopy was used to determine the regioregularity of the polymer composites, whereas Fourier transform infrared spectroscopy and differential scanning calorimetry were used to study their structural and thermal properties. Moreover, cyclic voltammetry was employed to evaluate the HOMO levels of the nanocomposites, while optical spectrophotometry (UV-Vis-NIR) was utilized to determine the optical bandgap of the composites. The information from the aforementioned techniques was used to estimate the HOMO-LUMO energy levels. The results revealed changes in the optical bandgap of P3HT with increasing graphene content. Furthermore, an extensive study aiming at the effect of graphene content on...

Nanostructural materials increase mineralization in bone cells and affect gene expression through miRNA regulation

We report that several nanomaterials induced enhanced mineralization (increased numbers and larger areas of mineral nests) in MC3T3‐E1 bone cells, with the highest response being induced by silver nanoparticles (AgNPs). We demonstrate that AgNPs altered microRNA expression resulting in specific gene expression associated with bone formation. We suggest that the identified essential transcriptional factors and bone morphogenetic proteins play an important role in activation of the process of mineralization in bone cells exposed to AgNPs.

Single-walled carbon nanotube and graphene nanodelivery of gambogic acid increases its cytotoxicity in breast and pancreatic cancer cells.

Graphene and single‐walled carbon nanotubes were used to deliver the natural low‐toxicity drug gambogic acid (GA) to breast and pancreatic cancer cells in vitro, and the effectiveness of this complex in suppressing cellular integrity was assessed. Cytotoxicity was assessed by measuring lactate dehydrogenase release, mitochondria dehydrogenase activity, mitochondrial membrane depolarization, DNA fragmentation, intracellular lipid content, and membrane permeability/caspase activity. The nanomaterials showed no toxicity at the concentrations used, and the antiproliferative effects of GA were significantly enhanced by nanodelivery. The results suggest that these complexes inhibit human breast and pancreatic cancer cells grown in vitro. This analysis represents a first step toward assessing their effectiveness in more complex, targeted, nanodelivery systems. Copyright

Raman spectroscopy as a detection and analysis tool for in vitro specific targeting of pancreatic cancer cells by EGF‐conjugated, single‐walled carbon nanotubes

Single‐walled carbon nanotubes (SWCNTs) were covalently linked to epidermal growth factor (EGF) proteins through an esterification process that was found to be responsible for the docking of SWCNTs on the human pancreatic cancer cells (PANC‐1) surface, thus providing a mechanism for the enhanced delivery and internalization of the nanotubes. Micro Raman spectroscopy and enzyme‐linked immunosorbent assay were used to evaluate the delivery process and kinetics of the SWCNTs. In vitro studies indicated that the delivery kinetics of SWCNT–EGF conjugates, at a concentration of 85 µg ml−1, to the PANC‐1 cell surfaces was significant in the first 30 min of incubation, but reached a plateau with time in accordance with the establishment of equilibrium between the association and the dissociation of EGF with the cell receptors. SWCNT–EGF conjugates could act as strong thermal ablation agents and could induce higher percentages of cellular death compared with the nontargeted SWCNTs alone. Copyright