Gd-GQDs as nanotheranostic platform for the treatment of HPV-positive oropharyngeal cancer.

In this study, we developed new gadolinium-graphene quantum dot nanoparticles (Gd-GQDs) as a theranostic platform for magnetic resonance imaging and improved the efficiency of radiotherapy in HPV-positive oropharyngeal cancer. Based on cell toxicity results, Gd-GQD NPs were nontoxic for both cancer and normal cell lines up to 25 µg/ml. These NPs enhance the cytotoxic effect of radiation only on cancer cells but not on normal cells. The flow cytometry analysis indicated that cell death mainly occurred in the late phase of apoptosis. The immunocytochemical analysis was used to evaluate apoptosis pathway proteins. The Bcl-2 and p53 protein levels did not differ statistically significantly between radiation alone group and those that received irradiation in combination with NPs. In contrast, the combination group exhibited a significant increase in Bax protein expression, suggesting that cells could undergo apoptosis independent of the p53 pathway. Magnetic resonance (MR) imaging showed that Gd-GQD NPs, when used at low concentrations, enhanced T1-weighted signal intensity resulting from T1 shortening effects. At higher concentrations, the T2 shortening effect became predominant and was able to decrease the signal intensity. Gd-GQD appears to offer a novel approach for enhancing the effectiveness of radiation treatment and facilitating MR imaging for monitoring HPV-positive tumors.

Improving the selective naked-eye detection of COVID-19 mediated by simultaneously using three different target oligonucleotides coated on plasmonic AuNPs/hexagonal Ag@AuNPs.

The localized surface plasmon resonance (LSPR) phenomenon provides a versatile property in biosensor technology. This uncommon feature was utilized to produce a homogeneous optical biosensor to detect COVID-19 by the naked-eye readout. In this work, we synthesized two types of plasmonic nanoparticles: (i) AuNPs and (ii) hexagonal core-shell nanoparticles-Au shell on AgNPs (Au@AgNPs). We report herein the development of two colorimetric biosensors employing the efficient targeting and the binding ability for three regions of the COVID-19 genome, that is, S-gene, N-gene and E-gene, at the same time. Two AuNPs and Ag@AuNPs individually coated with three different targets oligonucleotide sequence (TOs) (AuNPs-TOs-mix and Ag@AuNPs-TOs-mix) for simultaneous detection of S-gene, N-gene and E-gene of the COVID-19 virus, using the LSPR and naked-eye methods in the laboratory and biological samples. The target COVID-19 genome RNA detected using the AuNPs-TOs-mix and Ag@AuNPs-TOs-mix can achieve the same sensitivity. The detection ranges by the AuNPs-TOs-mix and Ag@AuNPs-TOs-mix are both sufficiently improved in equal amounts in comparison to any of the AuNPs-TOs and Ag@AuNPs-TOs. The sensitivity of the current COVID-19 biosensors were 94% and 96% based on the number of positive samples detected for AuNPs-TOs-mix and Ag@AuNPs-TOs-mix, respectively. Moreover, all the real-time PCR confirmed negative samples obtained the same results by the biosensor; accordingly, the specificity of this approach got to 100%. The current study reports a selective, reliable, reproducible and visual 'naked-eye' detection of COVID-19, devoid of the requirement of any sophisticated instrumental techniques.Communicated by Ramaswamy H. Sarma.

Alprazolam Detection Using an Electrochemical Nanobiosensor Based on AuNUs/Fe-Ni@rGO Nanocomposite.

Despite all the psychological advantages of alprazolam, its long list of toxic properties and interactions has caused concern and highlighted the need for a reliable sensing method. In this study, we developed a simple, highly sensitive electrochemical nanobiosensor to determine the desirable dose of alprazolam, averting the undesirable consequences of overdose. Gold nanourchins (AuNUs) and iron-nickel reduced graphene oxide (Fe-Ni@rGO) were immobilized on a glassy carbon electrode, which was treated beforehand. The electrode surface was characterized using cyclic voltammetry, Fourier transform infrared spectroscopy, scanning electron microscopy/energy-dispersive X-ray spectroscopy, and differential pulse voltammetry. The fabricated sensor showed two linear ranges (4 to 500 µg L-1 and 1 to 50 mg L-1), low limit of detection (1 µg L-1), high sensitivity, good repeatability, and good recovery. Increased -OH and carboxyl (-COOH) groups on the electrode surface, resulting in improved the adsorption of alprazolam and thus lower limit of detection. This nanobiosensor could detect alprazolam powder dissolved in diluted blood serum; we also studied other benzodiazepine drugs (clonazepam, oxazepam, and diazepam) with this nanobiosensor, and results were sensible, with a significant difference.

Comprehensive review on ultrasound-responsive theranostic nanomaterials: mechanisms, structures and medical applications.

The field of theranostics has been rapidly growing in recent years and nanotechnology has played a major role in this growth. Nanomaterials can be constructed to respond to a variety of different stimuli which can be internal (enzyme activity, redox potential, pH changes, temperature changes) or external (light, heat, magnetic fields, ultrasound). Theranostic nanomaterials can respond by producing an imaging signal and/or a therapeutic effect, which frequently involves cell death. Since ultrasound (US) is already well established as a clinical imaging modality, it is attractive to combine it with rationally designed nanoparticles for theranostics. The mechanisms of US interactions include cavitation microbubbles (MBs), acoustic droplet vaporization, acoustic radiation force, localized thermal effects, reactive oxygen species generation, sonoluminescence, and sonoporation. These effects can result in the release of encapsulated drugs or genes at the site of interest as well as cell death and considerable image enhancement. The present review discusses US-responsive theranostic nanomaterials under the following categories: MBs, micelles, liposomes (conventional and echogenic), niosomes, nanoemulsions, polymeric nanoparticles, chitosan nanocapsules, dendrimers, hydrogels, nanogels, gold nanoparticles, titania nanostructures, carbon nanostructures, mesoporous silica nanoparticles, fuel-free nano/micromotors.

Curcumin loaded on graphene nanosheets induced cell death in mammospheres from MCF-7 and primary breast tumor cells.

Elimination of tumor cells is still a therapeutic challenge for breast cancer (BC) in men and women. Mammospheres serve as valuablein vitrotools for evaluating tumor behavior and sensitivity to anticancer treatments. Graphene nanosheets with unique physicochemical properties have been considered as potential biomedical approaches for drug delivery, bioimaging, and therapy. Graphene oxide (GO) and graphene quantum dots (GQDs) are suitable nanocarriers for hydrophobic and low bioaccessible anti-tumor materials like curcumin. Despite extensive studies on the potential application of graphene nanosheets in medicine, our knowledge of how different cells function and respond to these nanoparticles remains limited. Here, we evaluated cell death in mammospheres from MCF-7 and primary tumor cells in response to curcumin loaded on graphene nanosheets. Mammospheres were exposed to graphene oxide-curcumin (GO-Cur) and graphene quantum dots-curcumin (GQDs-Cur), and the incidence of cell death was evaluated by Hoechst 33342/propidium iodide double staining and flow cytometry. Besides, the expression of miR-21, miR-29a, Bax, and Bcl-2 genes were assessed using RT-qPCR. We observed, GO, and GQDs had no cytotoxic effect on Kerman male breast cancer/71 (KMBC/71) and MCF-7 tumor cells, while curcumin induced death in more than 50% of tumor cells. GO-Cur and GQDs-Cur synergistically enhanced anti-tumor activity of curcumin. Moreover, GQDs-Cur induced cell death in almost all cells of KMBC/71 mammospheres (99%;p< 0.0001). In contrast, GO-Cur induced cell death in only 21% of MCF-7 mammosphere cells (p< 0.0001). Also, the expression pattern of miR-21, miR-29a, and Bax/Bcl-2 ratio in KMBC/71 and MCF-7 mammospheres was different in response to GO-Cur and GQDs-Cur. Although KMBC/71 and MCF-7 tumor cells had similar clinical features and displayed similar responses to curcumin, more investigations are needed to clarify the detailed molecular mechanisms underlying observed differences in response to GO-Cur and GQDs-Cur.

Organic dots (O-dots) for theranostic applications: preparation and surface engineering.

Organic dots is a term used to represent materials including graphene quantum dots and carbon quantum dots because they rely on the presence of other atoms (O, H, and N) for their photoluminescence or fluorescence properties. They generally have a small size (as low as 2.5 nm), and show good photostability under prolonged irradiation. The excitation and emission wavelengths of O-dots can be tailored according to their synthetic procedure, where although their quantum yield is quite low compared with organic dyes, this is partly compensated by their large absorption coefficients. A wide range of strategies have been used to modify the surface of O-dots for passivation, improving their solubility and biocompatibility, and allowing the attachment of targeting moieties and therapeutic cargos. Hybrid nanostructures based on O-dots have been used for theranostic applications, particularly for cancer imaging and therapy. This review covers the synthesis, physics, chemistry, and characterization of O-dots. Their applications cover the prevention of protein fibril formation, and both controlled and targeted drug and gene delivery. Multifunctional therapeutic and imaging platforms have been reported, which combine four or more separate modalities, frequently including photothermal or photodynamic therapy and imaging and drug release.

Nanomaterial integration into the scaffolding materials for nerve tissue engineering: a review.

The nervous system, which consists of a complex network of millions of neurons, is one of the most highly intricate systems in the body. This complex network is responsible for the physiological and cognitive functions of the human body. Following injuries or degenerative diseases, damage to the nervous system is overwhelming because of its complexity and its limited regeneration capacity. However, neural tissue engineering currently has some capacities for repairing nerve deficits and promoting neural regeneration, with more developments in the future. Nevertheless, controlling the guidance of stem cell proliferation and differentiation is a challenging step towards this goal. Nanomaterials have the potential for the guidance of the stem cells towards the neural lineage which can overcome the pitfalls of the classical methods since they provide a unique microenvironment that facilitates cell-matrix and cell-cell interaction, and they can manipulate the cell signaling mechanisms to control stem cells' fate. In this article, the suitable cell sources and microenvironment cues for neuronal tissue engineering were examined. Afterward, the nanomaterials that impact stem cell proliferation and differentiation towards neuronal lineage were reviewed.

Europium oxide nanorod-reduced graphene oxide nanocomposites towards supercapacitors.

Fast charge/discharge cycles are necessary for supercapacitors applied in vehicles including, buses, cars and elevators. Nanocomposites of graphene oxide with lanthanide oxides show better supercapacitive performance in comparison to any of them alone. Herein, Eu2O3 nanorods (EuNRs) were prepared through the hydrothermal method and anchored onto the surface of reduced graphene oxide (RGO) by utilizing a sonochemical procedure (in an ultrasonic bath) through a self-assembly methodology. The morphologies of EuNRs and EuNR-RGO were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and IR spectroscopy. Then, we used EuNRs and EuNR-RGO as electrode materials to investigate their supercapacitive behavior using cyclic voltammetry, galvanostatic charge-discharge, and electrochemical impedance spectroscopy techniques. In a 3.0 M KCl electrolyte and with a scan rate of 2 mV s-1, EuNR-RGO exhibited a specific capacity of 403 F g-1. Galvanostatic charge-discharge experiments demonstrated a specific capacity of 345.9 F g-1 at a current density of 2 A g-1. The synergy between RGO's flexibility and EuNR's high charge mobility caused these noticeable properties.

Ultrastructural and optical characteristics of cancer cells treated by a nanotechnology based chemo-photothermal therapy method.

The current chemotherapy method demonstrates the need for improvement in terms of efficacy and safety. Given the beneficiary effect of heat in combination with chemotherapy, the purpose of this study is to develop a multifunctional nanoplatform by co-incorporating gold nanoparticles (AuNPs) as photothermal agent and cisplatin as anticancer drug into alginate hydrogel (named as ACA) to enable concurrent thermo-chemotherapy. The in vitro cytotoxicity experiment showed that the as-developed nanocomplex was able to induce greater cytotoxicity in KB human nasopharyngeal cancer cells compared to free cisplatin at the same concentration. Moreover, the interaction of ACA and laser irradiation acted synergistically and resulted in higher cell death rate compared to separate application of photothermal therapy and chemotherapy. The micrograph of KB cells also revealed that ACA was able to selectively accumulate into the mitochondria, so that laser irradiation of KB cells pre-treated with ACA resulted in intensive morphological damages such as plasma membrane disruption, chromatin condensation, autophagic vacuoles formation and organelle degeneration. Moreover, the sign and magnitude of optical nonlinear refractive index measured by Z-scan technique was shown to be significantly altered in cells exposed to ACA with and without laser irradiation. Consequently, the nanocomplex developed herein could be a promising platform to combine photothermal therapy and chemotherapy effectively, thereby achieving synergistic therapeutic outcome.

A thermo-responsive alginate nanogel platform co-loaded with gold nanoparticles and cisplatin for combined cancer chemo-photothermal therapy.

The current interest in cancer research is being shifted from individual therapy to combinatorial therapy. In this contribution, a novel multifunctional nanoplatform comprising alginate nanogel co-loaded with cisplatin and gold nanoparticles (AuNPs) has been firstly developed to combine photothermal therapy and chemotherapy. The antitumor efficacy of the as-prepared nanocomplex was tested against CT26 colorectal tumor model. The nanocomplex showed an improved chemotherapy efficacy than free cisplatin and caused a significantly higher tumor inhibition rate. The in vivo thermometry results indicated that the tumors treated with the nanocomplex had faster temperature rise rate under 532 nm laser irradiation and received dramatically higher thermal doses due to optical absorption properties of AuNPs. The combined action of chemo-photothermal therapy using the nanocomplex dramatically suppressed tumor growth up to 95% of control and markedly prolonged the animal survival rate. Moreover, tumor metabolism was quantified by [18F]FDG (2-deoxy-2-[18F]fluoro-D-glucose)-positron emission tomography (PET) imaging and revealed that the combination of the nanocomplex and laser irradiation have the potential to eradicate microscopic residual tumor to prevent cancer relapse. Therefore, the nanocomplex can afford a potent anticancer efficacy whereby heat and drug can be effectively deliver to the tumor, and at the same time the high dose-associated side effects due to the separate application of chemotherapy and thermal therapy could be potentially reduced.

Optical assays based on colloidal inorganic nanoparticles.

Colloidal inorganic nanoparticles have wide applications in the detection of analytes and in biological assays. A large number of these assays rely on the ability of gold nanoparticles (AuNPs, in the 20 nm diameter size range) to undergo a color change from red to blue upon aggregation. AuNP assays can be based on cross-linking, non-cross linking or unmodified charge-based aggregation. Nucleic acid-based probes, monoclonal antibodies, and molecular-affinity agents can be attached by covalent or non-covalent means. Surface plasmon resonance and SERS techniques can be utilized. Silver NPs also have attractive optical properties (higher extinction coefficient). Combinations of AuNPs and AgNPs in nanocomposites can have additional advantages. Magnetic NPs and ZnO, TiO2 and ZnS as well as insulator NPs including SiO2 can be employed in colorimetric assays, and some can act as peroxidase mimics in catalytic applications. This review covers the synthesis and stabilization of inorganic NPs and their diverse applications in colorimetric and optical assays for analytes related to environmental contamination (metal ions and pesticides), and for early diagnosis and monitoring of diseases, using medically important biomarkers.

Facile sonochemical synthesis and morphology control of CePO4 nanostructures via an oriented attachment mechanism: application as luminescent probe for selective sensing of Pb²âº ion in aqueous solution.

CePO4 nanostructures with hexagonal phase were controllably synthesized using Ce(NO3)3 reaction with NH4H2PO4 through a sonochemical method by simply varying the reaction conditions. By adding ethanol and polyethylene glycol (PEG), coral-reef nanostructures (CRNs) were synthesized and controlling over pH caused to nanorods/nanowires. Oriented attachment (OA) is proposed as dominant mechanism on the growth of nanostructures which is in competition with Ostwald ripening (OR). The crystal structure and morphology of the nanostructures were characterized by X-ray diffraction (XRD) and field-emission scanning electron microscopy (FE-SEM), respectively. The luminescent properties of CePO4 with different morphologies have been studied. Among the nanostructures, nanoparticles with the highest intensity of fluorescent have been used as luminescent probe for selective sensing of Pb(2+) ion in aqueous solution.