Photothermal performance of a novel carbon dot and its conjugate with disulfiram for prostate cancer PC3 cell therapy.

Aim: To develop and employ a copper, sulfur, nitrogen-carbon quantum dot (C,S,N-CQD) multifunctional platform for synergistic cancer therapy, combining chemotherapy and photothermal treatment with in vitro cancer cell imaging. Materials & methods: Cu,S,N-CQDs were synthesized hydrothermally, loaded with disulfiram (DSF), and characterized through UV-Vis spectrophotometry, photoluminescence, Fourier-transform infrared spectroscopy, high-resolution transmission electron microscopy, dynamic light scattering, x-ray diffraction and EDAX. Results: Cu,S,N-CQD exhibited 5.5% absolute fluorescence quantum yield, 46.0% photothermal conversion efficiency and excellent stability. The release of DSF-loaded Cu,S,N-CQD, photothermal performance, and IC50 on PC3 prostate cancer cells, were evaluated. The impact of cellular glutathione on nanocarrier performance was investigated. Conclusion: Cu,S,N-CQD as a photothermal agent and DSF carrier showed synergy (combination index: 0.71) between chemotherapy and photothermal therapy. The nanocarrier simultaneously employed for in vitro cancer cell imaging due to its unique fluorescence properties.

Nanometer-scale particles can be used to treat and detect cancer in many ways. A type of nanoparticle was designed to attack cancer in two different ways. These nanoparticles ­ copper, sulfur, nitrogen­carbon quantum dots (C,S,N­CQDs) ­ were designed to both deliver a chemotherapy drug to cancer cells and act as a photothermal agent. This means that when light of a particular energy is shone on these particles, they heat up and can kill cancer cells. These C,S,N­CQDs loaded with the chemotherapy drug disulfiram were then tested on the prostate cancer cell line PC3. When a laser was shone on these particles and they became excited, they reduced cancer cell viability both by releasing the drug and heating up and killing the surrounding cells. These Cu,S,N-CQDs are also fluorescent, meaning they can be used to image cancer cells in tests like these.

A suitable drug structure for interaction with SARS-CoV-2 main protease between boceprevir, masitinib and rupintrivir; a molecular dynamics study.

In recent years, more than 200 countries of the world have faced a health crisis due to the epidemiological disease of COVID-19 caused by the SARS-CoV-2 virus. It had a huge impact on the world economy and the global health sector. Researchers are studying the design and discovery of drugs that can inhibit SARS-CoV-2. The main protease of SARS-CoV-2 is an attractive target for the study of antiviral drugs against coronavirus diseases. According to the docking results, binding energy for boceprevir, masitinib and rupintrivir with CMP are -10.80, -9.39, and -9.51 kcal/mol respectively. Also, for all investigated systems, van der Waals and electrostatic interactions are quite favorable for binding the drugs to SARS-CoV-2 coronavirus main protease, indicating confirmation of the complex stability.

Ultrasensitive FRET-based aptasensor for interleukin-6 as a biomarker for COVID-19 progression using nitrogen-doped carbon quantum dots and gold nanoparticles.

A label-free and specific FRET-based interleukin-6 (IL-6) aptasensor was developed using a DNA aptamer modified with nitrogen-doped carbon quantum dots (NCDs) and gold nanoparticles (AuNPs) as a donor-quencher pair. The assayed target was capable of disrupting the donor-acceptor assemblies yielding a concentration-related fluorescence recovery of NCDs (λem = 445 nm and λex = 350 nm). By designing two different probes, the interaction of DNA aptamers with IL-6 protein was studied using FRET efficiency. It appeared that the sensing probes showed slightly different sensing profiles. One of the aptasensors showed a linear response of 1.5-5.9 pg/mL for IL-6 with a coefficient of determination of R2 ≥ 0.99 and the a detection limit of 0.82 pg/mL (at S/N = 3). The experimental results indicated that the biosensor can be applied to determine IL-6 in human serum (with recovery of 95.7-102.9%). Due to the high sensitivity, excellent selectivity, and simplicity of the procedure, this strategy represents a promising alternative for IL-6 sensing in clinical applications.

Carbon quantum dots-Annexin V probe: photoinduced electron transfer mechanism, phosphatidylserine detection, and apoptotic cell imaging.

An annexin V-based probe is designed and fabricated using carbon quantum dot as highly stable and biocompatible fluorescent crystals for real-time fluorescence imaging of apoptotic cells. Carbon quantum dots were synthesized, characterized, and conjugated to annexin V. The fluorescence of CQDs at 450 nm (excitation at 350 nm) is quenched due to the photoinduced electron transfer between "carbon quantum dots" and two amino acids (tyrosine and tryptophan) in the annexin structure as quencher. The probe shows very strong and bright fluorescence emission in the presence of phosphatidylserine on the outer layer of the apoptotic cell membrane. It was shown that using fluorescence spectroscopy, the probe can be applied to sensitive phosphatidylserine determination and using fluorescence microscopy, it is possible to monitor cell apoptosis in real time.

Hairpin oligosensor using SiQDs: Förster resonance energy transfer study and application for miRNA-21 detection.

MicroRNAs are known to be tumor suppressors and promoters and can be used as cancer markers. In this work, a novel oligosensor was designed using Si quantum dots (SiQDs) for the detection of miRNAs. Five-nanometer SiQDs were synthesized, with a band gap of 2.8 eV, fluorescence lifetime of 4.56 µs (τ1/2 = 3.26 µs), quantum yield of 25%, fluorescence rate constant of 6.25 × 104, and non-radiative rate constant of 1.60 × 105 s-1. They showed excellent water dispersibility, good stability (with 95% confidence for 6-month storage) without photobleaching, and high biocompatibility, with an IC50 value of 292.2 µg/L. The SiQDs and Black Hole Quencher-1 (BHQ1) were conjugated to the 5' and 3' terminals of an oligomer, respectively. The resulting hairpin molecular beacon showed resonance energy transfer efficiency of 63%. A distance of 0.91 R (Förster distance) between SiQD and BHQ1 was obtained. In the presence of a stoichiometric amount of the complementary oligonucleotide (ΔGhybridization = -35.09 kcal mol-1), 98% of the fluorescence was recovered due to loop opening of the hairpin structure. The probe showed good selectivity toward miRNA-21, with a limit of detection of 14.9 fM. The oligosensor recoveries of miRNA-21 spiked in human serum and urine were 94-98% and 93-108%, respectively.

Label-free triplex DNA-based biosensing of transcription factor using fluorescence resonance energy transfer between N-doped carbon dot and gold nanoparticle.

Herein, a new turn-on fluorescent assay was established as a platform for the sensing of transcription factor NF-kB p50 based on triplex DNA labeled with N-doped carbon dots (NCDs) and gold nanoparticles (AuNPs) as donors and acceptors, respectively in the fluorescence resonance energy transfer (FRET) system. The synthetized nanoparticles were studied by different characterization techniques. A labeled DNA molecule was designed to form a triplex when no target protein existence and reported its formation by the change in FRET efficiency. While the triplex DNA was formed, the fluorescence of carbon dots at 503 nm (excitation at 460 nm) was quenched by FRET between NCD and AuNP. However, presence of NF-kB p50 followed by the considerable enhancement in the fluorescence intensity caused by the release of AuNPs labeled single stranded DNA from the triplex DNA structure, used for sensitive determination of the transcription factor. This technique showed a linearity (R2 = 0.9943) in the range of 20-150 pM with a limit of detection of 9 pM for the determination of NF-kB p50. Moreover, the sequence-specific triplex-based biosensor could discriminate NF-kB p50 from the other proteins with high selectively. Our results suggest that the biosensor provides a generalizable platform for rapid detection of NF-kB p50 in synthetic medium, promising in prevention and early diagnosis of cancer.

Warfarin Induced Quenching of the Carbon Quantum Dots: Mechanism Study and Warfarin Sensor Construction.

The mechanism of the fluorescence quenching of the CQDs by warfarin was determined and based on this study a simple, low cost and highly sensitive nanosensor was developed for determination of Warfarin in plasma samples. The carbon quantum dots with 3.5 µs lifetime (halflife of 2.4 µs) were synthesized by hydrothermal method and characterized. The fluorescence rate constant of 4.5 × 104 s-1 and quenching rate constant of 6.18 × 104 s-1 (from 10 µM warfarin that result in 17% lifetime reduction) was calculated. High quenching efficiency results in 21.63 L mmol-1 Stern-Volmer constant and the study of pH and temperature also confirm the dynamic quenching mechanism. The second order rate constant of 6.18 × 104 L mmol-1 s-1 was obtained for collisions between CQDs and warfarin. Based on this mechanism, a simple, low cost and very sensitive warfarin nanosensor was developed with calibration sensitivity of 21.63 L mmol-1, working range of 0.10 - 12.00 µM and detection limit of 0.01 µM.

Carbon dots-embedded N-acetylneuraminic acid and glucuronic acid-imprinted polymers for targeting and imaging of cancer cells.

Diagnosis, treatment, and prediction of cancer progression require new targeting agents to specifically target cell surface receptors. Herein, we demonstrated fluorescent carbon quantum dots-molecularly imprinted polymer (CQD-MIP) for selective targeting and imaging of cancer cells. Carbon quantum dots (CQDs) were synthesized and characterized. The synthesized CQDs had average size of 1.5 nm and show intense fluorescence emission at wavelength of 450 nm with excitation at 370 nm. CQD-MIP nanoparticles imprinted with N-acetylneuraminic acid and glucuronic acid were prepared and characterized. CQD-MIPs were successfully applied for selective targeting and imaging of MCF-7, HepG-2, and NIH-3T3 cell lines. Non-imprinted polymer (NIP) showed no binding properties toward a target molecule. Non-imprinted polymer (NIP) and non-cancerous human cell lines were used for controlling the imprinting and targeting effects, respectively. Acceptable results were obtained with imprinted polymers on cancer cells.

Biodegradation of Alprazolam in Pharmaceutical Wastewater Using Mesoporous Nanoparticles-Adhered Pseudomonas stutzeri.

The release of pharmaceutical wastewaters in the environment is of great concern due to the presence of persistent organic pollutants with toxic effects on environment and human health. Treatment of these wastewaters with microorganisms has gained increasing attention, as they can efficiently biodegrade and remove contaminants from the aqueous environments. In this respect, bacterial immobilization with inorganic nanoparticles provides a number of advantages, in terms of ease of processing, increased concentration of the pollutant in proximity of the cell surface, and long-term reusability. In the present study, MCM-41 mesoporous silica nanoparticles (MSN) were immobilized on a selected bacterial strain to remove alprazolam, a persistent pharmaceutical compound, from contaminated water. First, biodegrading microorganisms were collected from pharmaceutical wastewater, and Pseudomonas stutzeri was isolated as a bacterial strain showing high ability to tolerate and consume alprazolam as the only source for carbon and energy. Then, the ability of MSN-adhered Pseudomonas stutzeri bacteria was assessed to biodegrade alprazolam using quantitative HPLC analysis. The results indicated that after 20 days in optimum conditions, MSN-adhered bacterial cells achieved 96% biodegradation efficiency in comparison to the 87% biodegradation ability of Pseudomonas stutzeri freely suspended cells. Kinetic study showed that the degradation process obeys a first order reaction. In addition, the kinetic constants for the MSN-adhered bacteria were higher than those of the bacteria alone.

Synthesis of folic acid conjugated photoluminescent carbon quantum dots with ultrahigh quantum yield for targeted cancer cell fluorescence imaging.

Folic acid functionalized carbon quantum dots (FA-CQDs) with ultrahigh quantum yield (50 %) were synthesized by one-pot hydrothermal route using citric acid. The synthesized CQDs were characterized by fluorescence spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS) and X-ray diffraction. The cell viability of about 95 % and 97 % were obtained for MTT assay of the CQDs and FA-CQDs toward MCF-7 cells after 24 h of incubation respectively. The FA-CQDs were successfully applied for targeted imaging of ovarian cancer (type HeLa) and human breast adenocarcinoma (type MCF7) cells using fluorescence microscope.

Carbon quantum dots fluorescence quenching for potassium optode construction.

Photophysical phenomena associated with carbon nanoparticles in combination with biocompatibility and readily functionalizable properties have attracted significant interest for sensing and imaging applications. A potassium ion optode based on the fluorescence quenching of carbon quantum dots (CQDs) was constructed. The CQDs were synthesized using a microwave method, citric acid and 2,2'-(ethylene-dioxy)bis(ethylamine). A quantum yield of 7.1% was calculated for the synthesized CQDs. A linear dynamic range of about one-order of magnitude with a correlation coefficient of 0.99 was obtained. The optode was applied on real samples and a 0.60-1.60% error range was obtained relative to the ion-selective electrode.

A carbon dot and molecular beacon based fluorometric sensor for the cancer marker microRNA-21.

A carbon quantum dot (CQD) labeled molecular beacon was synthesized and applied to the detection of microRNA-21. The CQDs possess low cytotoxicity, excellent water solubility, and photostability. The CQDs were characterized by transmission electron microscopy, dynamic light scattering, Fourier-transform infrared spectroscopy, and fluorescence spectroscopy. The molecular beacon (MB) was labeled with the CQDs at the 5' end, and with Black Hole Quencher 1 (BHQ1) at the 3' end. The two labels act as the donor and acceptor parts of a FRET system, respectively. Only weak fluorescence is observed in the absence of microRNA-21, and in the presence of scrambled or mismatched sequences. However, in the presence of microRNA-21, fluorescence intensity of the CQDs at 460 nm (excitation at 360 nm) recovers. The hybridization of the hairpin structure of the MB with microRNA-21 opens the loop of MB. Consequently, the distance between the BHQ1 quencher and the CQDs is increased and fluorescence changes. The probe has high sensitivity (with a 0.3 nM limit of detection) and specificity. It can distinguish between microRNA-21 and its single mismatch mutant and hence represents a valuable tool for the early cancer diagnosis. Graphical abstract Schematic presentation of a fluorometric microR-21 assay using carbon dots carrying a molecular beacon (MB) labeled with a black hole quencher. Quenching is suppressed once the MB binds to microRNA-21.

Micro-RNA detection based on fluorescence resonance energy transfer of DNA-carbon quantum dots probes.

Carbon quantum dots have been proposed as an effective platform for miRNA detection. Carbon dots were synthesized by citric acid. The synthesized dots were characterized by dynamic light scattering, UV-Vis spectrophotometry, spectrofluorimetry, transmission electron microscopy and FT-IR spectrophotometry. The fluorescence quantum yield of the synthesized dots was determined using quinine sulfate as the standard. The FAM-labeled single stranded DNA, as sensing element, was adsorbed on dots by π-π interaction. The quenching of the dots fluorescence due to fluorescence resonance energy transfer (FRET) was used for mir 9-1 detection. In the presence of the complementary miRNA, the FRET did not take place and the fluorescence was recovered.

Localized surface plasmon resonance based gold nanobiosensor: Determination of thyroid stimulating hormone.

An immunoassay method based on the peak shift of the localized surface plasmon resonance (LSPR) absorption maxima has been developed for the determination of the thyroid stimulating hormone (TSH) in human blood serum. The anti-TSH antibody was adsorbed on the synthesized gold nanoparticles by electrostatic forces. The efficiency of the nanobiosensor was improved by optimizing the factors affecting the probe construction such as the pH and the antibody to gold nanoparticles ratio. Dynamic light scattering was applied for the characterization of the constructed probe. The amount of peak shift of the LSPR absorption maxima was selected as the basis for determination of TSH antigen. The linear dynamic range of 0.4-12.5 mIU L-1 and the calibration sensitivity of 1.71 L mIU-1 were obtained. The human control serum sample was analyzed for TSH by constructed nanobiosensor and the acceptable results were obtained.

Development of a localized surface plasmon resonance-based gold nanobiosensor for the determination of prolactin hormone in human serum.

A localized surface plasmon resonance immunoassay has been developed to determine prolactin hormone in human serum samples. Gold nanoparticles were synthesized, and the probe was prepared by electrostatic adsorption of antibody on the surfaces of gold nanoparticles. The pH and the antibody-to-gold nanoparticle ratio, as the factors affecting the probe functions, were optimized. The constructed nanobiosensor was characterized by dynamic light scattering. The sensor was applied for the determination of prolactin antigen concentration based on the amount of localized surface plasmon resonance peak shift. A linear dynamic range of 1-40 ng ml(-1), a detection limit of 0.8 ng ml(-1), and sensitivity of 10 pg ml(-1) were obtained. Finally, the nanobiosensor was applied for the determination of prolactin in human control serum sample.

Development of a partial least-squares calibration model for simultaneous determination of elements by inductively coupled plasma-atomic emission spectrometry.

A partial least-squares (PLS) calibration model was developed for simultaneous multicomponent elemental analysis with inductively coupled plasma-atomic emission spectrometry (ICP-AES) in the presence of spectral interference. The best calibration model was obtained using a PLS2 algorithm. Validation was performed with an artificial test set. Multivariate calibration models were constructed using 2 series of synthetic mixtures (Zn, Cu, Fe, and U, V). Accuracy of the method was evaluated with unknown synthetic and real samples.

Prediction of acute in vivo toxicity of some amine and amide drugs to rats by multiple linear regression, partial least squares and an artificial neural network.

The oral acute in vivo toxicity of 32 amine and amide drugs was related to their structural-dependent properties. Genetic algorithm-partial least-squares and stepwise variable selection was applied to select of meaningful descriptors. Multiple linear regression (MLR), artificial neural network (ANN) and partial least square (PLS) models were created with selected descriptors. The predictive ability of all three models was evaluated and compared on a set of five drugs, which were not used in modeling steps. Average errors of 0.168, 0.169 and 0.259 were obtained for MLR, ANN and PLS, respectively.