Amir Yadegari

Functionalized R9–reduced graphene oxide as an efficient nano-carrier for hydrophobic drug delivery

Loading of hydrophobic drugs on smart carbon nano-carriers is a challenging issue for developing advanced drug delivery systems. We introduced a novel, stable, functionalized, and targeted graphene-based drug delivery system for smart transportation of hydrophobic agents. For this purpose, the planar size of graphene oxide (GO) sheets was initially engineered using ultra-sonic waves under controlled conditions. The sonication treatment not only tuned the GO sheet sizes, but also led to formation of desired reactive groups, appropriate for developing functionalized and targeted drug carriers. Afterwards, the hydrothermal reaction was simultaneously employed for both grafting R9 peptides and reduction of GO sheets. Therefore, the produced functional structure is an R9–rGO complex with proper stability in physiological solutions and also with a high-performance loading capability of Paclitaxel (PX). The in vitro experiments revealed that the R9–rGO–PX compound was efficiently uptook by Hela cancer cell lines, and reduced the viability of Hela and MCF-7 cells more than 90% after 72 hours. The proposed approach has the advantage of green production of an applicable graphene-based drug delivery system for improving the smart transportation of hydrophobic anti-cancer drugs.

Wound dressing application of pH-sensitive carbon dots/chitosan hydrogel

Monitoring the pH of wounds has been recognized as an essential diagnosis factor during the healing process. This study presents a novel chitosan–carbon dots nanocomposite with dual applications as an antibacterial and pH-sensitive nano-agent for enhancing wound healing and monitoring the pH at the same time. The carbon dots (CDs) were synthesized using ammonium hydrogen citrate under hydrothermal conditions. The chitosan-based nanocomposites with different concentrations of CDs were fabricated through a solvent casting method. After detailed material characterization of the CDs and chitosan/CDs nanocomposites, the antibacterial activities and cell viability were thoroughly investigated against the Staphylococcus aureus bacterial species and L929 fibroblastic cell lines, respectively. The results indicated that the chitosan/CDs nanocomposites were biocompatible and nontoxic with effective antibacterial properties. The mechanical properties of the chitosan/CDs nanocomposite were improved via the addition of the CDs. The results show that the preparation of the chitosan/CDs nanocomposite at a concentration of 1.0 wt% carbon dots possessed the best optical, biological and mechanical characteristics. Furthermore, the results reveal that the proposed chitosan/CDs nanocomposites had outstanding pH-sensitive properties. According to the strong antibacterial properties and nontoxicity, as well as outstanding pH-sensitive nature, the proposed chitosan/CDs nanocomposites, as a smart materiel, have great potential applications in tissue engineering. Furthermore, the optimized ratio of CDs/chitosan nanocomposite was used as an antibacterial wound healing bandage and in vivo experiments were carried out on three groups of rats. The results showed that the CDs/chitosan nanocomposite not only possessed high pH sensitivity, but could also improve the wound healing process due to its antibacterial properties.

Normalization of doxorubicin release from graphene oxide: New approach for optimization of effective parameters on drug loading

Graphene oxide (GO) has been recently introduced as a suitable anticancer drug carrier, which could be loaded with doxorubicin (DOX) as a general chemotherapy agent. Herein, the attempts were made to optimize the effective parameters on both loading and release of DOX on GO. GO and GO–DOX were characterized using transition electron microscopy , zeta potential, Raman spectroscopy, UV–visible spectroscopy, and Fourier transform infrared spectroscopy. In addition, loading and releasing behaviors of DOX on GO were studied in terms of different temperature and pH values. The primary optimized values of pH and temperature for best‐loaded amount of DOX were 8.9 and 309 K, respectively. Moreover, we found that the smallest amount of released DOX, in pH of cancer microenvironment (5.4), occurs when DOX had been previously loaded in pH 7.8 and 310 K. Although the highest amount of loaded DOX was in basic pH, the results of efficient release of DOX from the GO–DOX complex and also cellular toxicity assay revealed that the best pH for loading of DOX on GO was 7.8. Therefore, in addition to optimization of parameters for efficient loading of DOX on GO, this study suggested that normalization of a released drug compared with the amount of a loaded drug could be a new approach for optimization of drug loading on nanocarriers.

An electrochemical cytosensor for ultrasensitive detection of cancer cells using modified graphene–gold nanostructures

The ultrasensitive detection of human prostate metastatic cancer cells (Du-145) was investigated through a novel electrochemical cytosensor. The proposed biosensor was simultaneously developed via two approaches: multivalent identification and signal amplification. Herein, anti-CD166 monoclonal antibody-modified gold electrode was applied to capture and recognize target cells (Du-145). Also, a graphene (G)/gold nanoparticle (GNP)/horseradish peroxidase (HRP)-conjugated trastuzumab antibody (G/GNP/Ab-HRP) hybrid nanostructure was designed as a nanoprobe for accurate recognition of target cells and efficient amplification of enzymatic signals simultaneously. The performance of the cytosensor could be significantly improved by utilizing this novel signal-amplification strategy. The cytosensor described here exhibited an appropriate cell-capture ability, broad range of detection, and exceptional sensitivity with a low limit of detection (20 cells). The fabricated cytosensor showed high sensitivity and selectivity for detection of Du-145 cancer cells while keeping an extended linear range from 102 to 106 cells per ml, and a conveniently low limit of detection of 20 cells per ml. The extraordinary analytical performance of this cytosensor indicates that it has a great potential for the detection of cancer cells and cancer stem cells.

Nitrogen doped nanoporous graphene: an efficient metal-free electrocatalyst for the oxygen reduction reaction

The oxygen reduction reaction (ORR) is an important half reaction, which occurs at the cathode within a fuel cell and limits their range of applications due to slow electrochemical kinetics. To overcome this issue, electrocatalysts are sought, which need to be an alternative to expensive and unsustainable metallic catalysts. Herein we report the synthesis of nitrogen doped nanoporous graphene (NPG), which is a competitive alternative to currently employed metallic catalysts. The NPG is synthesised through a chemical vapour deposition methodology followed by a chemical functionalization step introducing oxygen functional groups (carbonyl and hydroxyl groups), which is then doped with nitrogen via ortho-phenylenediamine (OPDA). The NPG is physiochemically and electrochemically characterised. The NPG demonstrates outstanding electrocatalytic activity towards the ORR in alkaline media proceeding via a favourable 4-electron pathway and is comparable to commercially available platinum–carbon (20%). We demonstrate that the electrochemical activity of the NPG is tailorable such that through increased nitrogen doping the ORR transforms from a 2-electron process to that of the favourable 4-electron process via increasing the proportion of pyridinic nitrogen while the content of graphitic nitrogen remains almost constant. The NPG exhibits excellent electrochemical performance towards the ORR in alkaline media, long-term stability and appropriate methanol crossover as benchmarked to commercialised Pt/C electrodes; this outstanding electrocatalytic activity is related to the high proportion of defects, high porosity and (pyridinic) doping.

Collagenous matrix supported by a 3D-printed scaffold for osteogenic differentiation of dental pulp cells

OBJECTIVE A systematic characterization of hybrid scaffolds, fabricated based on combinatorial additive manufacturing technique and freeze-drying method, is presented as a new platform for osteoblastic differentiation of dental pulp cells (DPCs). METHODS The scaffolds were consisted of a collagenous matrix embedded in a 3D-printed beta-tricalcium phosphate (β-TCP) as the mineral phase. The developed construct design was intended to achieve mechanical robustness owing to 3D-printed β-TCP scaffold, and biologically active 3D cell culture matrix pertaining to the Collagen extracellular matrix. The β-TCP precursor formulations were investigated for their flow-ability at various temperatures, which optimized for fabrication of 3D printed scaffolds with interconnected porosity. The hybrid constructs were characterized by 3D laser scanning microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and compressive strength testing. RESULTS The in vitro characterization of scaffolds revealed that the hybrid β-TCP/Collagen constructs offer superior DPCs proliferation and alkaline phosphatase (ALP) activity compared to the 3D-printed β-TCP scaffold over three weeks. Moreover, it was found that the incorporation of TCP into the Collagen matrix improves the ALP activity. SIGNIFICANCE The presented results converge to suggest the developed 3D-printed β-TCP/Collagen hybrid constructs as a new platform for osteoblastic differentiation of DPCs for craniomaxillofacial bone regeneration.

A genosensor for detection of HTLV-I based on photoluminescence quenching of fluorescent carbon dots in presence of iron magnetic nanoparticle-capped Au

Carbon dots and Fe3O4@Au were synthesized to develop a new biosensor to detect DNA target. We investigated the photoluminescence property of carbon dots (CDs) in the presence of Fe3O4-capped Au (Fe3O4@Au). Firstly, we designed two dedicated probes for unique long sequence region of human T-lymphotropic virus type 1 genome. One of the probes was covalently bound to the CDs. In the absence of target, CDs-probe was adsorbed on the surface of Fe3O4@Au through two possible mechanisms, leading to quenching the fluorescence emission of CDs. The fluorescence emission of CDs was recovered in the presence of target since double-stranded DNA cannot adsorb on the Fe3O4@Au. Also, Fe3O4@Au can adsorb the unhybridized oligonucleotides and improves the accuracy of detection. The specificity of the proposed biosensor was confirmed by BLAST search and assessed by exposing the biosensor to other virus targets. The experimental detection limit of the biosensor was below 10 nM with linear range from 10 to 320 nM.

Dual Porosity Protein-based Scaffolds with Enhanced Cell Infiltration and Proliferation

Abstract3D dual porosity protein-based scaffolds have been developed using the combination of foaming and freeze-drying. The suggested approach leads to the production of large, highly porous scaffolds with negligible shrinkage and deformation compared to the conventional freeze-drying method. Scanning electron microscopy, standard histological processing and mercury intrusion porosimetry confirmed the formation of a dual network in the form of big primary pores (243 ± 14 µm) embracing smaller secondary pores (42 ± 3 µm) opened onto their surface, resembling a vascular network. High interconnectivity of the pores, confirmed by micro-CT, is shown to improve diffusion kinetics and support a relatively uniform distribution of isolated human dental pulp stem cells within the scaffold compared to conventional scaffolds. Dual network scaffolds indicate more than three times as high cell proliferation capability as conventional scaffolds in 14 days.

Development of 3D printed PLGA/TiO2 nanocomposite scaffolds for bone tissue engineering applications

Porous scaffolds were 3D-printed using poly lactic-co-glycolic acid (PLGA)/TiO2 composite (10:1 weight ratio) for bone tissue engineering applications. Addition of TiO2 nanoparticles improved the compressive modulus of scaffolds. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) revealed an increase in both glass transition temperature and thermal decomposition onset of the composite compared to pure PLGA. Furthermore, addition of TiO2 was found to enhance the wettability of the surface evidenced by reducing the contact angle from 90.5 ± 3.2 to 79.8 ± 2.4 which is in favor of cellular attachment and activity. The obtained results revealed that PLGA/TiO2 scaffolds significantly improved osteoblast proliferation compared to pure PLGA (p < 0.05). Furthermore, osteoblasts cultured on PLGA/TiO2 nanocomposite showed significantly higher ALP activity and improved calcium secretion compared to pure PLGA scaffolds (p < 0.05).

Early diagnosis of disease using microbead array technology: A review

Early diagnosis of diseases (before they become advanced and incurable) is essential to reduce morbidity and mortality rates. With the advent of novel technologies in clinical laboratory diagnosis, microbead-based arrays have come to be recognized as an efficient approach, that demonstrates useful advantages over traditional assay methods for multiple disease-related biomarkers. Multiplexed microbead assays provide a robust, rapid, specific, and cost-effective approach for high-throughput and simultaneous screening of many different targets. Biomolecular binding interactions occur after applying a biological sample (such as blood plasma, saliva, cerebrospinal fluid etc.) containing the target analyte(s) to a set of microbeads with different ligand-specificities that have been coded in planar or suspension arrays. The ligand-receptor binding activity is tracked by optical signals generated by means of flow cytometry analysis in the case of suspension arrays, or by image processing devices in the case of planar arrays. In this review paper, we discuss diagnosis of cancer, neurological and infectious diseases by using optically-encoded microbead-based arrays (both multiplexed and single-analyte assays) as a reliable tool for detection and quantification of various analytes.