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A simple, one-pot and green method is reported for hydrothermal synthesis of highly fluorescent and magnetic carbon dots (CDs) by using D-glucose, as the carbon source. CDs were fully characterized by the UV-Vis and fluorescence spectroscopy, DLS, FTIR, TEM, EDS, XRD, and VSM. The nitrogen doping of different diamines significantly improved the fluorescence quantum yield (QY) of CDs with the maximum effect obtained by using m-phenylenediamine (mPDA). Temperature and reaction time also affected the QY of CDs with the best results obtained at 150 °C for 3 h. The heteroatom doping by innovative use of different metal sulfates including FeSO 4 , MnSO 4 , CuSO 4 , MgSO 4 , and ZnSO 4 , further improved the optical properties of CDs. Interestingly, the magnetic and multicolor CDs with high colloidal stability and QYs of 17.7, 16.5, and 53.9% at 460, 490, and 515 nm, respectively, were synthesized by using 0.1 M of glucose, mPDA and MnSO 4 . The resulted Mn-, S-, N-doped CDs represented rapid uptake and high-quality fluorescence imaging of the human fibroblast and umbilical vein endothelial cells in vitro, without significant toxicity. The CDs also displayed high r 1 relaxivity of 32.3 mM - 1 s - 1 and were used for high-contrast MR and fluorescence imaging of mouse tumor models, in vivo., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Microbubbles, inside-out microdroplets, act as extraordinary microreactors to facilitate thermodynamically unfavorable reactions in bulk solutions of water. We explored the formation of hydrogen peroxide (H 2 O 2 ) and its sustained regeneration at the interface of water-gas microbubbles. For this purpose, the chemiluminescence of luminol was recorded by a digital camera to map the intensity of blue light emission over the time of about 20 min. The formation and regeneration of hydrogen peroxide were also monitored by fluorescence microscopic imaging of a hydrogen peroxide probe. The microscopic images consistently show a stable glow around the microbubbles over time during which the formed hydrogen peroxide diffuses into the bulk solution. This observation confirms that the concentration of H 2 O 2 at the interface is 30 times higher than that in the water solution bulk after several minutes, which can be attributed to its regeneration at the water-gas interface. These findings increase our understanding of why the chemistries of gas microbubbles in water and water microdroplets surrounded by gas are so distinct from those of bulk-phase water.

A straightforward nebulized spray system is designed to explore the hydrogenation of carbon dioxide (CO 2 ) within water microdroplets surrounded by different gases such as carbon dioxide, nitrogen, oxygen, and compressed air. The collected droplets are analyzed using water-suppressed nuclear magnetic resonance (NMR). Formate anion (HCOO - ), acetate anion (CH 3 COO - ), ethylene glycol (HOCH 2 CH 2 OH), and methane (CH 4 ) are detected when water is nebulized. This pattern persisted when the water is saturated with CO 2 , indicating that CO 2 in the nebulizing gas triggers the formation of these small organics. In a pure CO 2 atmosphere, the formate anion concentration is determined to be ≈70 µm, referenced to dimethyl sulfoxide, which has been introduced as an internal standard in the collected water droplets. This study highlights the power of water microdroplets to initiate unexpected chemistry for the transformation of CO 2 to small organic compounds., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Using real-time mass spectrometric (MS) monitoring, we demonstrate one-step, catalyst-free spontaneous oxidation of various alcohols (ROH) to key reactive intermediates for the formation of ROO - compounds on the surface of water microdroplets surrounded by alcohol vapor, carried out under ambient conditions. These organic peroxides (POs) can act as important secondary organic aerosols (SOA). We used hydrogen-deuterium exchange by spraying D 2 O instead of H 2 O to learn about the reaction mechanism, and the results demonstrate the crucial role of the water-air interface in microdroplet chemistry. We find that the formation of POs relies on electron transfer occurring at the microdroplet interface, which generates hydrogen atoms and hydroxyl radicals that lead to a cascade of radical reactions. This electron transfer is believed to be driven by two factors: (1) the emergence of a strong electrostatic potential on the microdroplet's surface; and (2) the partial solvation of ions at the interface. Mass spectra reveal that the formation of POs is dependent on the alcohol structure, with tertiary alcohols showing a higher tendency to form organic peroxides than secondary alcohols, which in turn are more reactive than primary alcohols.

Packaging is very important to maintain the quality of food and prevent the growth of microbes. Therefore, the use of food packaging with antimicrobial properties protects the food from the growth of microorganisms. In this study, antibacterial nanocomposite films of polyvinyl alcohol/starch/chitosan (PVA/ST/CS) together with nickel oxide-copper oxide nanoparticles (NiO-CuONPs) are prepared for food packaging. NiO-CuONPs were synthesized by the co-precipitation method, and structural characterization of nanoparticles (NPs) was carried out by XRD, FTIR, and SEM techniques. Composites of PVA/ST/CS, containing different percentages of NPs, were prepared by casting and characterized by FTIR and FESEM. The mechanical properties, diffusion barrier, and thermal stability were determined. The nanoparticles have a round structure with an average size of 6.7 ± 1.2 nm. The cross-section of PVA/ST/CS film is dense, uniform, and without cracks. In the mechanical tests, the addition of NPs up to 1% improved the mechanical properties (TS = 31.94 MPa), while 2% of NPs lowered TS to 14.76 MPa. The fibroblast cells toxicity and the films antibacterial activity were also examined. The films displayed stronger antibacterial effects against Gram-positive bacteria (Staphylococcus aureus) compared to Gram-negative bacteria (Escherichia coli). Furthermore, these films have no toxicity to fibroblast cells and the survival rate of these cells in contact with the films is more than 84%. Therefore, this film is recommended for food packaging due to its excellent mechanical and barrier properties, good antibacterial activity, and non-toxicity., (© 2024. The Author(s).)

Water microdroplets (7 to 11 µm average diameter, depending on flow rate) are sprayed in a closed chamber at ambient temperature, whose relative humidity (RH) is controlled. The resulting concentration of ROS (reactive oxygen species) formed in the microdroplets, measured by the amount of hydrogen peroxide (H 2 O 2 ), is determined by nuclear magnetic resonance (NMR) and by spectrofluorimetric assays after the droplets are collected. The results are found to agree closely with one another. In addition, hydrated hydroxyl radical cations (•OH-H 3 O + ) are recorded from the droplets using mass spectrometry and superoxide radical anions (•O 2 - ) and hydroxyl radicals (•OH) by electron paramagnetic resonance spectroscopy. As the RH varies from 15 to 95%, the concentration of H 2 O 2 shows a marked rise by a factor of about 3.5 in going from 15 to 50%, then levels off. By replacing the H 2 O of the sprayed water with deuterium oxide (D 2 O) but keeping the gas surrounding droplets with H 2 O, mass spectrometric analysis of the hydrated hydroxyl radical cations demonstrates that the water in the air plays a dominant role in producing H 2 O 2 and other ROS, which accounts for the variation with RH. As RH increases, the droplet evaporation rate decreases. These two facts help us understand why viruses in droplets both survive better at low RH values, as found in indoor air in the wintertime, and are disinfected more effectively at higher RH values, as found in indoor air in the summertime, thus explaining the recognized seasonality of airborne viral infections., Competing Interests: Competing interests statement:The authors declare no competing interest.

Food packaging with antibacterial properties has attracted much attention recently. In this study, nickel oxide nanoparticles (NiONPs) were synthesized by co-precipitation and then gelatin/chitosan polymer films (GEL/CS) with different percentages of NiONPs, bio-nanocomposites, were prepared by casting. Morphology, crystal microstructure, molecular interactions and thermal stabilities of the NPs and the composite films were characterized by FESEM, XRD, FTIR and TGA, respectively. The bio-nanocomposite films exhibited excellent barrier, thermal and mechanical properties by addition of an optimized content of NPs. For example, the tensile strength (TS) of the GEL/CS film without NPs was 23.83 MPa and increased to 30.13 MPa by incorporation of 1% NPs. The antibacterial properties and toxicity of the films were investigated. These films show good antibacterial behavior against Gram-positive (Staphylococcus aureus) bacteria compared to Gram-negative (Escherichia coli) bacteria. Furthermore, the films were found to be non-toxic to fibroblast cells that came into contact with the films, with a survival rate of more than 88%. Therefore, these films can be applied for food packaging due to their excellent mechanical, barrier, and antibacterial properties., (© 2024. The Author(s).)

Chemoradiotherapy with controlled-release nanocarriers such as sono-sensitive nanodroplets (NDs) can enhance the anticancer activity of chemotherapy medicines and reduces normal tissue side effects. In this study, folic acid-functionalized methotrexate-loaded perfluorohexane NDs with alginate shell (FA-MTX/PFH@alginate NDs) were synthesized, characterized, and their potential for ultrasound-guided chemoradiotherapy of breast cancer was investigated in vitro and in vivo. The cancer cell (4T1) viabilities and surviving fractions after NDs and ultrasound treatments were significantly decreased. However, this reduction was much more significant for ultrasound in combination with X-ray irradiation. The in vitro and in vivo results confirmed that MTX-loaded NDs are highly biocompatible and they have no significant hemolytic activity and organ toxicity. Furthermore, the in vivo results indicated that the FA-MTX/PFH@alginate NDs were accumulated selectively in the tumor region. In conclusion, FA-functionalized MTX/PFH@alginate NDs have a great theranostic performance for ultrasound-controlled drug delivery in combination with radiotherapy of breast cancer., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Facile and sensitive detection and isolation of circulating tumor cells (CTCs) was achieved using the aptamer-targeted magnetic nanoparticles (Apt-MNPs) in conjugation with a microfluidic device. Apt-MNPs were developed by the covalent attachment of anti-MUC1 aptamer to the silica-coated magnetic nanoparticles via the glutaraldehyde linkers. Apt-MNPs displayed high stability and functionality after 6 months of storage at 4 °C. The specific microfluidic device consisting of mixing, sorting and separation modules was fabricated through conventional photo- and soft-lithography by using polydimethylsiloxane. The capture efficiency of Apt-MNPs was first studied in vitro on MCF-7 and MDA-MB-231 cancer cell lines in the bulk and microfluidic platforms. The cell capture yields of more than 91% were obtained at the optimum condition after 60 minutes of exposure to 50 μg mL -1 Apt-MNPs with 10 to 10 6 cancer cells in different media. CTCs were also isolated efficiently from the blood samples of breast cancer patients and successfully propagated in vitro . The isolated CTCs were further characterized using immunofluorescence staining. The overall results indicated the high potential of the present method for the detection and capture of CTCs., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Ultrapure N 2 gas was bubbled through water, and the humidified output containing undetectable concentrations of ozone filled a closed chamber in which 18 MΩ-cm water was sprayed through a silica capillary to form microdroplets. Analysis of the collected microdroplets by NMR spectroscopy showed the presence of hydrogen peroxide at a concentration level ranging from 0.3 to 1.5 μM depending on the flow conditions. This was confirmed using a spectrofluorometric assay. We suggest that this finding establishes that when sprayed to form microdroplets, water has the ability to produce hydrogen peroxide by itself. When the N 2 gas is replaced by compressed air or O 2 gas, the concentration of hydrogen peroxide is found to increase, indicating that gas-surface interactions with O 2 in aqueous microdroplets promote the formation of hydrogen peroxide.

Regarding the cancer fatal consequences, early detection and progression monitoring are the most vital issues in patients' treatment and mortality reduction. Therefore, there is a great demand for fast, inexpensive, and selective detection methods. Herein, a graphene-based aptasensor was designed for sensitive human breast cancer cell detection. A reduced graphene oxide-chitosan-gold nanoparticles composite was used as a biocompatible substrate for the receptor stabilization. The significant function of the aptamer on this composite is due to the synergistic effects of the components in improving the properties of the composite, including increasing the electrical conductivity and effective surface area. After the aptasensor incubation in MCF-7 cancer cells, the cell membrane proteins interacted specifically with the three dimensional-structure of the AS1411 aptamer, resulting in the cell capture on the aptasensor. The aptasensor fabrication steps were investigated by cyclic voltammetry and electrochemical impedance spectroscopy. The higher cell concentrations concluded to the higher captured cells on the aptasensor which blocked the Ferro/Ferricyanide access to the sensor, causing increases in the charge transfer resistances. This aptasensor shows a linear relationship with the cell concentration logarithm, high selectivity, a wide linear range of 1 × 10 1 -1 × 10 6 cells/mL, and a low detection limit of 4 cells/mL., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Dual-modal molecular imaging by combining two imaging techniques can provide complementary information for early cancer diagnosis and therapeutic monitoring. In the present manuscript, folic acid (FA)-functionalized gadolinium-loaded nanodroplets (NDs) are introduced as dual-modal ultrasound (US)/magnetic resonance (MR) imaging contrast agents. These phase-change contrast agents (PCCAs) with alginate (Alg) stabilizing shell and a liquid perfluorohexane (PFH) core were successfully synthesized via the nano-emulsion method and characterized. In this regard, mouse hepatocellular carcinoma (Hepa1-6) as target cancer cells and mouse fibroblast (L929) as control cells were used. The in vitro and in vivo cytotoxicity assessments indicated that Gd/PFH@Alg and Gd/PFH@Alg-FA nanodroplets are highly biocompatible. Gd-loaded NDs do not induce organ toxicity, and no significant hemolytic activity in human red blood cells is observed. Additionally, nanodroplets exhibited strong ultrasound signal intensities as well as T 1 -weighted MRI signal enhancement with a high relaxivity value of 6.40 mM -1  s -1 , which is significantly higher than that of the clinical Gadovist contrast agent (r 1  = 4.01 mM -1  s -1 ). Cellular uptake of Gd-NDs-FA by Hepa1-6 cancer cells was approximately 2.5-fold higher than that of Gd-NDs after 12 h incubation. Furthermore, in vivo results confirmed that the Gd-NDs-FA bound selectively to cancer cells and were accumulated in the tumor region. In conclusion, Gd/PFH@Alg-FA nanodroplets have great potential as US/MR dual-modal imaging nanoprobes for the early diagnosis of cancer., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aim: To develop a novel theranostic nanoplatform for simultaneous fluorescent monitoring and stimuli-triggered drug delivery. Materials & methods: Different microscopic and spectroscopic techniques were used for the characterization of nanocarriers. MCF-7 and human umbilical vein endothelial cell lines were cultured and treated with different doses of doxorubicin-loaded nanocarriers. The cell viability and drug release were studied using MTT assay and fluorescence microscopy. Results: Biocompatible and mono-disperse nanocarriers represent hollow and mesoporous structures with the calculated surface area of 552.83 m 2 .g -1 , high magnetic activity (12.6 emu.g -1 ), appropriate colloidal stability and high drug loading capacity (up to 61%). Conclusion: Taxane-based carbon dots act as the pH-responsive gatekeepers for the controlled release of doxorubicin into cancer cells and provide a fluorescence resonance energy transfer system for real-time monitoring of drug delivery.

In the present study, the effect of functionalized gold nanoclusters (AuNCs) with trastuzumab (Herceptin®) and/or folic acid (FA) as a single and dual-targeted radiosensitizers for the enhancement of megavoltage radiation therapy efficacy was investigated. SK-BR3 breast cancer cells as human epidermal growth factor 2 (HER2) and folate overexpressing cell line and the murine fibroblast (L929) as a control cell line were selected. The cellular uptake was followed using inductively coupled plasma optical emission spectrometry (ICP-OES) that showed AuNCs-FA-HER uptake by SK-BR3 cells was 3 times more than the non-targeted AuNCs after 12 h incubation. MTT and clonogenic assays revealed that the viability and surviving fraction of cancer cells were significantly inhibited by treating with all AuNCs under radiation compared to treating with radiation alone. However, these effects in the dual-targeted AuNCs group (AuNCs-FA-HER) was significantly greater than non-targeted and single-targeted AuNCs groups. Also, apoptosis was evaluated using an Annexin V-FITC/propidium iodide (PI) kit in flow cytometry. All AuNCs, in combination with 4 Gy of photon beam, induced more apoptosis. By fitting the survival fraction data on the linear-quadratic model, the sensitization enhancement factor (SER) of AuNCs, AuNCs-FA, AuNCs-HER, and AuNCs-FA-HER, were obtained 1.17, 1.32, 1.48 and 1.77, respectively. SER for AuNCs-FA-HER was significantly higher than that non-targeted and single-targeted AuNCs (p-value < 0.05) that can be attributed to more internalization in the cancer cells. It was concluded that functionalized AuNCs with both folic acid and Herceptin could represent a promising strategy for increased cellular internalization that improved radiation therapy efficiency in SK-BR3 breast cancer cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

G-rich oligonucleotide, AS1411, has been shown to interact with nucleolin and to inhibit cancer cell proliferation and tumor growth. This antiproliferative action is increased when AS1411 is conjugated to different types of nanoparticles. However, the molecular mechanisms are not known. In this work, we show in several cell lines that optimized AS1411-conjugated gold nanoparticles (GNS-AS1411) inhibit nucleolin expression at the RNA and protein levels. We observed an alteration of the nucleolar structure with a decrease of ribosomal RNA accumulation comparable to what is observed upon nucleolin knock down. However, the expression of genes involved in cell cycle and the cell cycle blockage by GNS-AS1411 are not regulated in the same way as that in cells where nucleolin has been knocked down. These data suggest that the anti-proliferative activity of GNS-AS1411 is not the only consequence of nucleolin targeting and down-regulation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A sensitive prostate-specific antigen (PSA) detection method using a visual-readout closed bipolar electrode (BPE) system has been introduced by integration of hydrogen evolution reaction (HER) in cathodic pole and electrochemiluminescence (ECL) of luminol loaded within the MIL-53(Fe)-NH 2 (L@MIL-53(Fe)-NH 2 ) in the anodic pole. The cathode of the BPE was electrochemically synthesized by 3D porous copper foam, followed by decorating with nitrogen-doped graphene nanosheet and ruthenium nanoparticles. As an alternative, we employed carboxylate-modified magnetic nanoparticles (MNPs) for immobilization of the primary antibody (Ab1) and utilized the L@MIL-53(Fe)-NH 2 conjugated to secondary antibody (Ab2) as a signaling probe and coreaction accelerator. After sandwiching the target PSA between Ab1 and Ab2, the MNP/Ab1-PSA-Ab2/L@MIL-53(Fe) were introduced to a gold anodic BPE. Finally, the resulting ECL of luminol and H 2 O 2 at the anodic poles was monitored using a photomultiplier tube (PMT) or digital camera. The PMT and visual (camera)-based detections showed linear responses from 1 pg mL -1 to 300 ng mL -1 (limit of detection 0.2 pg mL -1 ) and 5 pg mL -1 to 200 ng mL -1 (limit of detection 0.1 pg mL -1 ), respectively. This strategy provides an effective method for high-performance bioanalysis and opens a new door toward the development of the highly sensitive and user-friendly device.

Gold nanoparticles (GNPs) radiosensitizing effect strongly depends on the tumor targeting efficacy. The aim of this study is to identify the most ideal targeting decoration for BSA-GNPs according to tumor targeting and biodistribution. Therefore, three well-known targeting agents (folic acid, glucose, and glutamine) were utilized for BSA-GNPs decoration. Glucose-BSA-GNPs, glutamine-BSA-GNPs, and folic acid-BSA-GNPs were synthesized and then, characterized by Fourier-transform infrared spectroscopy and UV-Spectrometry. Then, the GNPs were intravenously injected 10 mg/kg to 4T1 breast tumor-bearing mice to evaluate biodistribution and radiosensitizing effects. Folic acid and glutamine decorations could significantly increase tumor targeting efficacy of BSA-GNPs as 2.1 and 2.4 times increase of gold accumulation was detected in comparison with BSA-GNPs. They exhibited the highest radiosensitizing efficacy and caused about 33% decrease in tumors volume in comparison with BSA-GNPs after 6 Gy radiation therapy. All the GNPs were completely biocompatible. Although, glutamine-BSA-GNPs and folic acid-BSA-GNPs could significantly enhance the tumor targeting and radiosensitizing efficacy of BSA-GNPs, did not exhibit any significant advantage over each other. Therefore, glutamine and folic acid decoration of BSA-GNPs can significantly increase the tumor targeting and therapeutic efficacy as radiosensitizer., (Copyright © 2019. Published by Elsevier B.V.)

In the present study, alive attenuated Salmonella typhi Ty21a was introduced as a vehicle for smart delivery of gold nanoparticles to the tumours' hypoxic regions. At the first step, the uptakes of gold nanoparticles with seven different decorations by S. typhi Ty21a was investigated using flow cytometry and inductively coupled plasma optical emission spectroscopy. The analyses demonstrated that folic acid functionalised gold nanoparticles (FA-GNPs) are the best candidates for producing the Golden Bacteria (GB). Subsequently, the GB and FA-GNPs efficacies for tumour targeting were investigated after intravenous injection to CT-26 tumour-bearing mice. The GB exhibited more GNPs delivery to the tumour in comparison with FA-GNPs. Moreover, GB injection causes more delivery of GNPs to the tumours' central regions in comparison with tumours' periphery. This trend is completely in reverse for FA-GNPs injected group. The ratios of peripheral to central regions' gold concentration of the tumours were 1.95 ± 0.13 and 0.61 ± 0.10 for FA-GNPs and GB groups, respectively. This observation demonstrates higher accumulation of gold nanoparticles in the centre of the tumour due to their active delivery by the S. typhi Ty21a to the deeps of tumours.

In the present manuscript, a new spectrofluorometric method for the genotyping of various single nucleotide polymorphisms (SNPs) using carbon dots (CDs) is investigated. For the construction of the assay, thiolated probe DNA is self-assembled on a gold surface via sulfur‑gold chemistry and afterward, the probe is partially hybridized with a longer target DNA strand. Subsequently, the unhybridized section of the target DNA is hybridized with a capture DNA to form the DNA double-helix self-assembled monolayer on the gold surface. Finally, CDs surface amine groups are covalently attached to the 5' phosphate groups of various monobases (MB-CDs) using phosphoramidite chemistry. In this method, genotyping of SNPs is based on following the changes in fluorescence intensity of the MB-CDs suspensions before and after incubation with DNA modified gold surface. The assay is straightforward with no need for target labeling and is sensitive and low cost enough to genotype various SNPs independent of their position in a DNA double helix with an acceptable limit of detections in picomolar ranges., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: One class of magnetic nanoparticles is magnetic iron oxide nanoparticles (MIONs) which has been widely offered due to of their many advantages. Owing to the extensive application of MIONs in biomedicine, before they can be used in vivo, their cytotoxicity have to be investigated. Therefore, there is an urgent need for understanding the potential risks associated with MIONs., Materials and Methods: Firstly, gold-coated Fe 3 O 4 nanoparticles (GMNP) were synthesized. The size, structure and spectroscopic properties of the nanoparticles were characterized by transmission electron microscopy (TEM), X-ray diffractometry (XRD) and UV-Visible spectrophotometer, respectively. Cytotoxicity of nanoparticles was studied with different concentrations ranging from 10 µg/mL up to 400 µg/mL and for different incubation times (12 hours and 24 hours) on MCF-7 and HFFF-PI6. Cytotoxicity study was performed by MTT assay., Results: XRD pattern confirmed the structure of GMNPs and TEM image shows that GMNPs are under 50 nm. For MCF-7 and HFFF-PI6 cells, at concentration of 300 and 400 µg/mL, Fe 3 O 4 nanoparticles are toxic, respectively. Moreover, for both cells, cell viability for GMNPs is higher than %80, therefore, up to 400 µg/mL they are not toxic. Results show that for both cells, Fe 3 O 4 nanoparticles have higher cytotoxicity than GMNPs., Conclusion: This finding suggests that gold coating reduces the toxic effects of uncoated Fe 3 O 4 nanoparticles. Less toxicity of GMNP may be attributed to controlled release from Fe 2+ ions in intracellular space. Moreover, cell toxicity increased with raise in dose (concentration) and incubation time.

Carbon dots (CDs), as a new generation of fluorescent nanoparticles, have been greatly considered for different biomedical applications. In the present study, a one-pot hydrothermal method was developed for the synthesis of a series of carbon dots (CDs) for cancer imaging and therapy. Taxane diterpenoids were utilized as the carbon source, different diamines were used as the nitrogen source, and folic acid was used as a targeting agent. High-quality photostable and multicolor (blue and green) carbon nanocrystals with a hexagonal shape, a narrow size distribution of less than 20 nm, and high fluorescence quantum yield of up to 50.4% were obtained from taxanes in combination with m -phenylenediamine and folic acid to give the best results. The nanoparticles displayed a potent anticancer activity with IC 50 values of 31.3 ± 2.7 and 34.1 ± 1.1 μg mL -1 for the human MCF-7 and HeLa cancer cell lines, respectively, and IC 50 value of 120.5 ± 3.8 μg mL -1 on the normal human fibroblast cells. The flow cytometry studies determined apoptosis-mediated cell death as the main anticancer mechanism of CDs, and the molecular studies revealed the induction of both extrinsic and intrinsic apoptosis pathways. The overall results indicated the great potential of synthesized CDs for the simultaneous cancer imaging and therapy.

In the present manuscript, a closed bipolar electrode system integrated with electrochemiluminescence (ECL) detection has been introduced for sensitive diagnosis of human breast cancer cells (MCF-7). For sensitive and selective detection, the anodic pole of the bipolar electrode was modified with the AS1411 aptamer, a specific aptamer for the nucleolin, and treated by the secondary aptamer modified gold nanoparticles. The electrochemiluminescence of luminol was followed in the presence of hydrogen peroxide on the anode pole of bipolar electrode (BPE) as an analytical signal. Moreover, 3D printed microchannels were used for the fabrication of BPE systems to minimize the required amounts of sample. The present aptasensor offers low cost, sensitive and selective cancer cell detection with two acceptable linear ranges. The first linear section appears within 10-100 cells and the latter is found to be within 100-700 cells. The limit of detection was about 10 cells., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: Herein, the AS1411 aptamer-targeted ultrasmall gold nanoclusters (GNCs) were assessed at different aspects as a radiosensitizer., Materials & Methods: AS1411 aptamer-conjugated gold nanoclusters (Apt-GNCs) efficacy was evaluated at cancer cells targeting, radiosensitizing effect, tumor targeting, and biocompatibility in breast tumor-bearing mice., Results: Flow cytometry and fluorescence microscopy exhibited more cellular uptake for Apt-GNCs in comparison with GNCs. In addition, inductively coupled plasma optical emission spectrometry results demonstrated its effective tumor targeting as the tumors' gold content for GNCs and Apt-GNCs were 8.53 and 15.33 μg/g, respectively. Apt-GNCs significantly enhanced radiotherapy efficacy as mean tumors' volume decreased about 39% and 9 days increase in the mice survival was observed. Both GNCs and Apt-GNCs were biocompatible., Conclusion: The Apt-GNCs is a novel and efficient  radiosensitizer.

Aptamers, due to the inherently high selectivity towards target analytes, are promising candidate for surface modification of the nanoparticles. Therefore, aptamer-functionalized magnetic nanoparticles (AMNPs) was prepared and used to develop a magnetic solid-phase extraction procedure for clean-up of milk and dairy products samples before measuring the aflatoxin M1 (AFM1) contents by the high-performance liquid chromatography. The prepared sorbent was characterized by different instrumental methods such as FT-IR, FESEM, TEM, EDX and AGFM. The AMNPs was used in extraction and pre-concentration of ultratrace amounts AFM1 from local milk samples. The amount of sorbent, elution volume, extraction time, and salt addition were optimized. Based on the results, calibration plot is linear over the 0.3 to 1 ng·L -1 and 5 to 50 ng·L -1 AFM1 concentration ranges. The limits of detection of the developed method were obtained 0.2 ng·L -1 which is the smallest value that has been reported up to now. The results show that this new superior sorbent has a large potential to simplify the complex matrix of the samples and can used for detection, preconcentration and accurate determination of ultratrace amounts of the AFM1 from milk and dairy products., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A sensitive electrochemiluminescence (ECL) aptasensor for aflatoxin M1 (AFM1) detection by a closed bipolar electrode (BPE) array has been introduced. The thiolated AFM1 aptamer was immobilized on gold nanoparticle-coated magnetic Fe 3 O 4 nanoparticles (Apt-GMNPs). Luminol-functionalized silver nanoparticle-decorated graphene oxide (GO-L-AgNPs) participates in π-π interactions with the unpaired bases of the immobilized aptamer (Apt-GMNPs-GO-L-AgNPs). After the Apt-GMNPs-GO-L-AgNPs were introduced to a gold anodic BPE array, the individual electrodes were subjected to different concentrations of AFM1. Upon the interaction of AFM1 with the aptamers, the GO-L-AgNPs detach from the aptamer; the resulting ECL of luminol and H 2 O 2 at the anodic poles is monitored using a photomultiplier tube (PMT) or smartphone, and the images are analyzed using ImageJ software. This process triggers thionine reduction at the cathodic poles. Under the optimal conditions obtained by a face-centered central composite design (FCCD), the PMT-based detection of the BPE-ECL aptasensor exhibit a linear response over a wide dynamic range from 5 to 150ngmL -1 , with a detection limit of 0.01ngmL -1 . Additionally, smartphone-based detection shows a linear relationship between the ECL image gray value and the logarithmic concentration of the AFM1 target over a range of 10-200ngmL -1 , with a detection limit of 0.05ngmL -1 . Furthermore, the BPE-ECL aptasensor was successfully used to detect AFM1 in milk complex media without any serious interferences with reliable reproducibility (average relative standard deviation (RSD = 2.3%)). This smartphone-based detection opens a new horizon for bioanalysis that does not require a trained technician to operate and is a promising technology for point-of-care testing., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In the present study, a nanoporous gold platform was applied for the amplified detection of Hepatitis B virus (HBV) by an electrochemical DNA biosensor. Ferrocene as a redox reporter was covalently attached to the DNA probe and its electrochemical signal was recorded as the biosensor response. For real samples, DNA was firstly extracted from blood of patients and then amplified by polymerase chain reaction (PCR) for 5cycles. Sensitivity of this biosensor was enhanced by using nanoporous gold electrode, therefore this sensor can discriminate the genome of HBV in real sample with low PCR cycles. By this strategy and signal amplification using nanoporous platform and covalently attached electroactive label, the biosensor can distinguish between healthy and HBV patients with limited PCR cycles. Moreover, the errors of PCR with large cycles can be disregarded. A linear dynamic range of 0.4 to 10nmol of mutant DNA was achieved, with reliable reproducibility (RSD) 8.9%., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In the present study, a sensitive and selective signal-on method for aptamer based spectrofluorometric detection of cancer cells is introduced. AS1411, a nucleolin aptamer, is wrapped around water-soluble carbon dots and used as a probe for the detection of several types of cancer cells. Nucleolin, is overexpressed on the surface of cancer cells. Mouse breast 4T1, human breast MCF7, and human cervical HeLa cancer cells were selected as target cells, while human foreskin fibroblast cells HFFF-PI6 served as control cells. For the sensitive and selective spectrofluorimetric detection of target cancer cells in the presence of control cells, the cells were incubated in carbon dots-aptamer solutions, the cell suspensions were subsequently centrifuged and the fluorescence intensities were measured as an analytical signal. The specific targeting of cancer cells by AS1411 aptamers causes the release of carbon dots and enhances the fluorescence intensity. A calibration curve with a dynamic range between 10-4500 4T1 cells and detectability of roughly 7 cells was obtained. In addition, no significant change in the signal was detected by modifying the amount of human foreskin fibroblast control cells. Our results demonstrate similar responses to human MCF7 breast and cervical HeLa cancer cells.

The increasing demands for early, accurate and ultrasensitive diagnosis of cancers demonstrate the importance of the development of new amplification strategies or diagnostic technologies. In the present study, an aptamer-based electrochemical biosensor for ultrasensitive and selective detection of leukemia cancer cells has been introduced. The thiolated sgc8c aptamer was immobilized on gold nanoparticles-coated magnetic Fe 3 O 4 nanoparticles (Apt-GMNPs). Ethidium bromide (EB), intercalated into the stem of the aptamer hairpin, provides the read-out signal for the quantification of the leukemia cancer cells. After introduction of the leukemia cancer cells onto the Apt-GMNPs, the hairpin structure of the aptamer is disrupted and the intercalator molecules are released, resulting in a decrease of the electrochemical signal. The immobilization of nitrogen-doped graphene nanosheets on the electrode surface provides an excellent platform for amplifying the read-out signal. Under optimal conditions, the aptasensor exhibits a linear response over a wide dynamic range of leukemia cancer cells from 10 to 1×10 6 cellmL -1 . The present protocol provides a highly sensitive, selective, simple, and robust method for early stage detection of leukemia cancer. Furthermore, the fabricated aptasensor was successfully used for the detection of leukemia cancer cells in complex media such as human blood plasma, without any serious interference., (Copyright © 2016. Published by Elsevier B.V.)

Early detection of breast cancer is the most effective way to improve the survival rate in women. Magnetic resonance imaging (MRI) offers high spatial resolution and good anatomic details, and its lower sensitivity can be improved by using targeted molecular imaging. In this study, AS1411 aptamer was conjugated to Fe 3 O 4 @Au nanoparticles for specific targeting of mouse mammary carcinoma (4T1) cells that overexpress nucleolin. In vitro cytotoxicity of aptamer-conjugated nanoparticles was assessed on 4T1 and HFFF-PI6 (control) cells. The ability of the synthesized nanoprobe to target specifically the nucleolin overexpressed cells was assessed with the MRI technique. Results show that the synthesized nanoprobe produced strongly darkened T 2 -weighted magnetic resonance (MR) images with 4T1 cells, whereas the MR images of HFFF-PI6 cells incubated with the nanoprobe are brighter, showing small changes compared to water. The results demonstrate that in a Fe concentration of 45 μg/mL, the nanoprobe reduced by 90% MR image intensity in 4T1 cells compared with the 27% reduction in HFFF-PI6 cells. Analysis of MR signal intensity showed statistically significant signal intensity difference between 4T1 and HFFF-PI6 cells treated with the nanoprobe. MRI experiments demonstrate the high potential of the synthesized nanoprobe as a specific MRI contrast agent for detection of nucleolin-expressing breast cancer cells., Competing Interests: There are no conflict of interest.

The development of simple, inexpensive, hand-held, user-friendly biosensor for high throughput and multiplexed genotyping of various single nucleotide polymorphisms (SNPs) in a single run experiment by a nonspecialist user is the main challenge in the analysis of DNA. Visualizing the signal and possibility to monitor SNPs by a digital camera opens a new horizon for the routine applications. In the present manuscript, a novel wireless electrochemiluminescence (ECL) DNA array is introduced for the visualized genotyping of different SNPs on the basis of ECL of luminol/hydrogen peroxide system on a bipolar electrode (BPE) array platform. After modification of anodic poles of the array with the DNA probe and its hybridization with the targets, genotyping of various SNPs is carried out by exposing the array to different monobase modified luminol-platinum nanoparticles (M-L-PtNPs). Upon the hybridization of M-L-PtNPs to mismatch sites, the ECL of luminol is followed using a photomultiplier tube (PMT) or digital camera and the images are analyzed by ImageJ software. This biosensor can detect even thermodynamically stable SNP (G-T mismatches) in the range of 2-600 pM. Also, by combining the advantages of BPE and the high visual sensitivity of ECL, it could be easily expected to achieve sensitive screening of different SNPs. The present biosensor demonstrates the capability for the discrimination between PCR products of normal, heterozygous, and homozygous beta thalassemia genetic disorders.

In the present manuscript, a strategy to prompt the sensitivity of a biosensor based on the dual amplification of signal by applying a nanoporous gold electrode (NPGE) as a support platform and soluble graphene oxide (GO) as an indicator has been developed. By increasing the surface area of the biosensing platform and because of unique GO/ss-DNA interactions, the sensitivity for the detection of SNPs is enhanced. In the presence of SNPs, because of less effective hybridization of mutant targets compared to complementary targets, further GO could adsorb on mutant targets-modified NPGE viaπ-π interactions, causing a large increase in the charge transfer resistance (Rct) of the electrode. This protocol provides a cost-effective and fast method for the discrimination of different SNPs. Furthermore, this biosensor can detect thermodynamically stable SNP (G-T mismatches) in the range of 15-1600 pM. The present strategy is a label-free and sensitive protocol and does not require sophisticated fabrication.

In this manuscript, the electrocatalytic reduction of hydrogen peroxides on Prussian blue (PB) modified nanoporous gold film (NPGF) electrode is described. The PB/NPGF is prepared by simple anodizing of a smooth gold film followed by PB film electrodeposition method. The morphology of the PB/NPGF electrode is characterized using scanning electron microscopy (SEM). The effect of solution pH and the scan rates on the voltammetric responses of hydrogen peroxide have also been examined. The amperometric determination of H2O2 shows two linear dynamic responses over the concentration range of 1μM-10μM and 10μM-100μM with a detection limit of 3.6×10(-7)M. Furthermore, this electrode demonstrated good stability, repeatability and selectivity remarkably., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Liver cancer is one of the most common cancers in the world and has no effective cure, especially in later stages. The development of a tangible protocol for early diagnosis of this disease remains a major challenge. In the present manuscript, an aptamer-based, label-free electrochemical biosensor for the sensitive detection of HepG2, a hepatocellular carcinoma cell line, is described. The target cells are captured in a sandwich architecture using TLS11a aptamer covalently attached to a gold surface and a secondary TLS11a aptamer. The application of TLS11a aptamer as a recognition layer resulted in a sensor with high affinity for HepG2 cancer cells in comparison with control cancer cells of human prostate, breast, and colon tumors. The aptasensor delivered a wide linear dynamic range over 1 × 10(2) to 1 × 10(6) cells/mL, with a detection limit of 2 cells/mL. This protocol provides a precise method for sensitive detection of liver cancer with significant advantages in terms of simplicity, low cost, and stability.

In spite of the promising applications of aptamers in the bioassays, the development of aptamer-based electrochemical biosensors with the improved limit of detection has remained a great challenge. A strategy for the amplification of signal, based on application of nanostructures as platforms for the construction of an electrochemical adenosine triphosphate (ATP) aptasensor, is introduced in the present manuscript. A sandwich assay is designed by immobilizing a fragment of aptamer on a nanoporous gold electrode (NPGE) and its association to second fragment in the presence of ATP. Consequently, 3, 4-diaminobenzoic acid (DABA), as a molecular reporter, is covalently attached to the amine-label of the second fragment, and the direct oxidation signal of DABA is followed as the analytical signal. The sensor can detect the concentrations of ATP as low as submicromolar scales. Furthermore, 3.2% decrease in signal is observed by keeping the aptasensor at 4 °C for a week in buffer solution, implying a desirable stability. Moreover, analog nucleotides, including GTP, UTP and CTP, do not show serious interferences and this sensor easily detects its target in deproteinized human blood plasma., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The application of a nanoporous gold electrode (NPGE) in the fabrication of an electrochemical sensing system for the detection of single base mismatches (SBMs) using ferrocene-modified DNA probe has been investigated in the present manuscript. Ferrocene carboxylic acid is covalently attached to the amino-modified probe using EDC/NHS chemistry. By covalent attachment of the redox reporter molecules on the top of DNA, the direct oxidation of the ferrocene on the electrode surface is avoided. On the other hand, the electrochemical signals are amplified by anodizing the electrode surface and converting it to nanoporous form. By improving the sensitivity of the biosensor, the different SBMs including the thermodynamically stable G-A and G-T mismatches, can be easily distinguished. In this research, NPGE was prepared by anodization and chemical reduction of Au surface and used for signal amplification. Nanoporous electrode enhances the sensitivity of DNA biosensor and makes it capable to detect complementary target DNA in sub-nanomole scales., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The capability of silver nanoparticles (SNP) as redox tag in the construction of an electrochemical aptasensor for the detection of adenosine triphosphate (ATP) is investigated in the present manuscript. To construct the aptasensor, a well-known ATP binding aptamer (ABA) splits into two segments. The first amino-labeled segment of the aptamer was covalently immobilized on 3-mercaptopropionic acid modified gold electrode surface by the formation of carbodiimide bond. The second segment was modified by SNPs and associated with the first segment in the presence of ATP. The direct oxidation signal of SNPs is followed as the analytical signal to detect ATP. The sandwich assay shows a suitable signal gain and importantly, a good response time. The sensor can detect the concentrations of ATP as low as micromolar scales with a desirable stability under optimum conditions. Furthermore, analog nucleotides including GTP, UTP and CTP, do not show serious interferences and this sensor readily detects its target in a complex media such as human blood plasma., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The present manuscript describes a label free electrochemical aptasensor for the detection of sodium diclofenac (DCF). In order to construct the biosensor, the amino-functionalized diclofenac binding aptamer (DBA) was covalently immobilized on the surface of the glassy carbon electrode (GCE). The conformation of the DBAs on the surface of the electrode is changed when this is exposed to different concentrations of DCF. The introduction of DCF induces an alteration in the conformation of the surface immobilized DBA and causes a decrease in the charge transfer resistance of the aptasensor. However, the charge transfer resistance is increased by incubation of GCE/DBA/DCF in the secondary DBA. The changes in the charge transfer resistance have been monitored using the voltammetric and electrochemical impedance spectroscopic (EIS) techniques. The aptasensor shows two different linear dynamic ranges over 0-5.0 μM and 10 μM to 1mM, and the sensitivity of 15.7 kΩ μM(-1) and detection limit of 2.7 × 10(-7)M were obtained. The validity of the method and applicability of the aptasensor were successfully evaluated by detection of DCF in a blood serum sample without interference from the sample matrix. Furthermore, the aptasensor has shown good stability., (Copyright © 2012 Elsevier B.V. All rights reserved.)

In this manuscript, a strategy for the amplification of the responses of an electrochemical DNA hybridization biosensor using silver nanoparticles (Ag-NPs) as redox reporters and its capability for the detection of a single base mismatches (SBM) including thermodynamically stable ones, is described. In this assay, Ag-NPs are immobilized on the top of recognition layer and their oxidation signals are followed. Differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) are used to monitoring the electrode response. Only for complementary target sequence, electron can transfer between Electrode surface and nanoparticles via DNA and Ag-NPs can be oxidized. Therefore this DNA biosensor could differentiate between complementary target and one containing either SBM or thermodynamically stable G-A and G-T targets through oxidation signal of Ag-NPs. This biosensor is able to detect SBM by overcome the direct electron transfer of redox reporter with electrode surface and positioning of it before the mismatch position., (Copyright © 2011 Elsevier B.V. All rights reserved.)

In this work, binding of two water soluble Schiff base complexes: Bis sodium (5-sulfosalicylaldehyde) o-phenylendiiminato) Manganese (III) acetate (Salophen complex) and Bis sodium (5-sulfosalicylaldehyde) 1, 2 ethylendiiminato) Manganese (III) acetate (Salen complex) with calf thymus (ct) DNA were investigated by using different spectroscopic and electrometric techniques including UV-vis, Circular dichroism (CD) and fluorescence spectroscopy, viscommetry and cyclic voltammetry (CV). Both complexes have shown a hyperchromic and a small bathochromic shift in the visible region spectra. A competitive binding study showed that the enhanced emission intensity of ethidium bromide (EB) in the presence of DNA was quenched by the addition of the two Schiff base complexes indicating that they displace EB from its binding site in DNA. Moreover structural changes in the CD spectra and an increase in the CV spectra with addition of DNA were observed. The results show that both complexes bind to DNA. The binding constants have been calculated using fluorescence data for two complexes also K(b) was calculated with fluorescence Scatchard plot for Salophen. Ultimately, the experimental results show that the dominant interactions are electrostatic while binding mode is surface binding then followed by hydrophobic interactions in grooves in high concentration of complexes., (© Springer Science+Business Media, LLC 2011)

The electrochemical behavior of electrodes made by sealing carbon nanofibers in glass or with electrophoretic paint has been studied by scanning electrochemical microscopy (SECM). Because of their small electroactive surface area, conical geometry with a low aspect ratio and high overpotential for proton and oxygen reduction, carbon nanofiber (CNF) electrodes are promising candidates for producing electrode nanogaps, imaging with high spatial resolution and for the electrodeposition of single metal nanoparticles (e.g., Pt, Pd) for studies as electrocatalysts. By using the feedback mode of the SECM, a CNF tip can produce a gap that is smaller than 20 nm from a platinum disk. Similarly, the SECM used in a tip-collection substrate-generation mode, which subsequently shows a feedback interaction at short distances, makes it possible to detect a single CNF by another CNF and then to form a nanometer gap between the two electrodes. This approach was used to image vertically aligned CNF arrays. This method is useful in the detection in a homogeneous solution of short-lifetime intermediates, which can be electrochemically generated at one electrode and collected at the second at distances that are equivalent to a nanosecond time scale.

The electrochemical behavior of Ce(III) ion in the presence of EDTA and their application for electrocatalytic oxidation of nitrite ion is described in this manuscript. The electrochemical properties of Ce(III)-EDTA complex as well as the two-electron oxidation of nitrite ion were investigated using cyclic voltammetry and hydrodynamic voltammetry methods. Kinetic parameters such as transfer coefficient, homogeneous rate constant for electrocatalytic oxidation of nitrite ion at the experimental conditions, were obtained. Also the possible mechanism for oxidation of nitrite ion using Ce(III)-EDTA complex is proposed. The detection limit of 4.8x10(-6)M and dynamic linear range 1.0x10(-5) to 1.0x10(-2)M were obtained for determination of nitrite ion using electrocatalytic oxidation of this ion by Ce(III)-EDTA complex.

The electrochemical behavior of cobalt hexacyanoferrate complex adsorbed on a carbon paste electrode (CPE) and its application to the electrocatalytic oxidation of guanine and single-strand DNA (ss-DNA) in aqueous solution are investigated in this report. The modification of CPE by the adsorption of this complex results in excellent amplification of the guanine oxidation response of ss-DNA. The effects of paste composition, scan rate, DNA, and guanine concentration were studied. The detection limits of 52 and 920 ng mL(-)(1) were obtained for guanine and ss-DNA, respectively.