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Raman Spectroscopic Analysis of Signaling Molecules–Dopamine Receptors Interactions in Living Cells
摘要： The selective interaction of signaling compounds including neurotransmitters and drugs with the dopamine receptors (DARs) is extremely important for the treatment of neurodegenerative diseases. Here, we report a method to probe the selective interactions of signaling compounds with D1 and D2 DARs in living cells using the combined approach of theoretical calculation and surface-enhanced Raman spectroscopy (SERS). When signaling compounds such as DA, amphetamine, methamphetamine, and methylenedioxypyrovalerone interact with D1 dopamine receptors (DRD1), the intracellular cyclic adenosine monophosphate (cAMP) level is increased. However, the intracellular level of cAMP is decreased when D2 dopamine receptors (DRD2) interact with the abovementioned signaling compounds. In our experiments, we have internalized the silica-coated silver nanoparticles (AgNP@SiO2) in living cells to adsorb biologically generated cAMP which was probed by using SERS. Besides adsorptions of cAMP, AgNP@SiO2 has a crucial role for the enhancement of Raman cross section of the samples. We observed the characteristic SERS peaks of cAMP when DRD1-overexpressed cells interact with the signaling compounds; these peaks were not observed for other cells including DRD2-overexpressed and DRD1?DRD2-coexpressed cells. Our experimental approach is successful to probe the intracellular cAMP and characterize the selectivity of signaling compounds to different types of DARs. Furthermore, our experimental approach is highly capable for in vivo studies because it can probe intracellular cAMP using a low input power of incident laser without significant cell damage. Our experimental results and density functional theory calculations showed that 780 and 1503 cm?1 are signature Raman peaks of cAMP. The SERS peak at 780 cm?1 is associated with C?O, C?C, and C?N stretching and symmetric and asymmetric bending of two O?H bonds of cAMP, whereas the SERS peak at 1503 cm?1 is contributed by the O9?H3 bending mode.
关键词： cyclic adenosine monophosphate,living cells,signaling compounds,dopamine receptors,surface-enhanced Raman spectroscopy
更新于2025-09-23 15:21:21
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<i>In Vitro</i> Ligand Binding Kinetics Explains the Pharmacokinetics of [ <sup>18</sup> F]FE-PE2I in Dopamine Transporter PET Imaging
摘要： Two of the most popular positron emission tomography (PET) tracers, [11C]PE2I and [18F]FE-PE2I, used to quantify dopamine transporters (DAT), display dissimilar kinetic behavior in in vivo assays. This difference can be explained by comparing values of kinetic rate constants, which characterize interaction of these tracers with DAT sites in vitro. At the same time, this kinetic analysis showed that the overall binding mechanism is similar for these two tracers and includes a fast step of complex formation followed by a slow isomerization step of this complex. Comparison with previous PE2I data revealed that isomerization of the DAT complex with PE2I occurs three times faster than in the case of FE-PE2I, which leads to the slower onset of peak specific binding of the former tracer in the DAT-rich regions. Therefore, ligands with slower isomerization on-rate, including [18F]FE-PE2I, seem to be better tracers in vivo, and their properties can be predicted in vitro.
关键词： isomerization,ligand binding kinetics,FE-PE2I,Dopamine transporter,DAT,PET,PE2I
更新于2025-09-23 15:21:21
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Quantitative Understanding of the Ultra-Sensitive and Selective Detection of Dopamine using Graphene Oxide/WS2 Quantum Dot Hybrid
摘要： Herein, we report on the ultra-high sensitive and selective detection of dopamine (DA) at pico-molar level by a low cost sensing platform based on graphene oxide (GO) sheets anchored with tungsten disulfide quantum dots (WS2 QDs). The liquid phase exfoliated WS2 QDs are mostly bilayer type with an average particle size ~2.0 ± 0.3 nm, while the GO sheets are of few-layer thickness. The WS2 QDs are highly luminescent with photoluminescence (PL) quantum yield of ~15% and they exhibit excitation wavelength dependent spectral shift in PL due to the high degree of edge/defect states. In presence of GO, the PL intensity of WS2 QDs partially quenches due to van der Waals interaction and excited-state charge transfer from WS2 to GO. However, in the presence of DA, drastic quenching of PL occurs for WS2/GO hybrid and this enables selective detection of DA as low as 10 pM, which is the lowest among the reported values. We present a new model to quantitatively explain the GO mediated efficient charge transfer and unusual quenching of PL as a function of the DA concentration. Finally, the WS2/GO based sensor is utilized for the detection of DA in the river water and blood serum with a satisfactory recovery, which establishes its practical utility as an efficient environmental/biochemical sensor.
关键词： Fluorescence Quenching,Dopamine,Biosensor,Graphene Oxide,WS2 Quantum Dots
更新于2025-09-23 15:21:01
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[O-methyl-11C]N-(4-(4-(3-Chloro-2-methoxyphenyl)-piperazin-1-yl)butyl)-1H-indole-2-carboxamide ([11C]BAK4-51) Is an Efflux Transporter Substrate and Ineffective for PET Imaging of Brain D3 Receptors in Rodents and Monkey
摘要： Selective high-affinity antagonists for the dopamine D3 receptor (D3R) are sought for treating substance use disorders. Positron emission tomography (PET) with an effective D3R radioligand could be a useful tool for the development of such therapeutics by elucidating pharmacological specificity and target engagement in vivo. Currently, a D3R-selective radioligand does not exist. The D3R ligand, N-(4-(4-(3-chloro-2-methoxyphenyl)piperazin-1-yl)butyl)-1H-indole-2-carboxamide (BAK4-51, 1), has attractive properties for PET radioligand development, including full antagonist activity, very high D3R affinity, D3R selectivity, and moderate lipophilicity. We labeled 1 with the positron-emitter carbon-11 (t1/2 = 20.4 min) in the methoxy group for evaluation as a radioligand in animals with PET. However, [11C]1 was found to be an avid substrate for brain efflux transporters and lacked D3R-specific signal in rodent and monkey brain in vivo.
关键词： dopamine D3 receptors,radiolabeling,PET,efflux transporter substrate,antagonist
更新于2025-09-23 15:21:01
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Aequorin as a sensitive and selective reporter for detection of dopamine: A photoprotein inhibition assay approach
摘要： Dopamine is a metabolite that plays a key role in the human body and in biomedical and diagnostic applications. Thus, the concentration of this analyte has been considered in various diseases in therapeutic drug monitoring (TDM). In the present study, for the first time, a photoprotein inhibition assay strategy was developed by utilizing aequorin for the direct detection of dopamine as a receptor and reporter simultaneously. The results showed that bioluminescence emission of aequorin was effectively quenched by increasing concentration of dopamine at the range of 1 nM to 100 μM with a detection limit of 53 nM. The viability of this method for the monitoring of dopamine in spiked biological fluids was also established and it was successfully applied for the direct determination of dopamine in a blood serum and urine without preliminary treatment with satisfactory quantitative recovery 90-95% and 82-93%, respectively. The structural investigation using circular dichroism, fluorescence spectroscopy, and docking simulation indicated that, changes in the microenvironment of aromatic residues were significant, while minor conformational alterations of the protein were observed. It seems dopamine inhibits bioluminescence activity with specific binding to the residues involved in the light production.
关键词： therapeutic drug monitoring,dopamine,aequorin,photoprotein inhibition assay
更新于2025-09-23 15:21:01
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Full Solution-Processed Fabrication of Conductive Hybrid Paper Electrodes for Organic Optoelectronics
摘要： There is growing interest in the development of “green” electronics fabricated from “natural” materials, which could lead to renewable, sustainable and potential inexpensive organic optoelectronics. In this paper, a novel, facile and full-solution processed approach has been successfully demonstrated to fabricate a highly flexible and conductive paper electrode by electroless deposition with the dopamine molecules as an adhesion layer on the newly hybrid paper. The novel paper substrate was prepared through simple hot-press with commercial paper and polypropylene (PP) film. And it has smooth surface and improved mechanical property. Importantly, it is flexible and highly resistant to water, which was important for solution process. The obtained highly conductive paper exhibited smooth and hydrophobic surface with high reflection. In addition, these conductive papers also showed excellent mechanical flexibility and stability, indicating the strong adhesion between metal and hybrid paper, which facilitates the roll-to-roll process of the device. As a possible application, this paper electrode can be effectively used as a mechanical support and electrode in organic light-emitting diode (OLED), showing the potential possibility in future electronics.
关键词： adhesion,dopamine,hybrid paper,electroless deposition,conductive
更新于2025-09-23 15:19:57
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Enhanced photoelectrocatalytic degradation of bisphenol A and simultaneous production of hydrogen peroxide in saline wastewater treatment
摘要： The degradation of organic pollutants in saline wastewater has been a challenge for environmental remediation. In this study, a two-chamber cell was structured to simultaneously degrade organic contaminants (bisphenol A, BPA) from saline wastewater and produce hydrogen peroxide (H2O2). In the anode chamber, a new solar-light-driven system was devised using chloride ions (Cl?) as a medium and WO3 photoanode as a radical initiator. Under solar light irradiation, photogenerated holes yielded at the WO3 photoanode promoted the conversion of Cl? to reactive chlorine species, which could oxidize BPA more rapidly. The results indicated that the BPA removal can be significantly enhanced by increasing pH to 10.8 or increasing the Cl? concentration to 200 mM. At these conditions, 92% BPA was degraded into CO2 and H2O in 120 min. In the cathode chamber, a new dopamine modified carbon felt (CF-DPA) cathode was employed to produce H2O2, obtaining a high concentration of 5.4 mM under optimum conditions. The electrochemical analyses for CF-DPA revealed that dopamine modification promoted electron transfer and enhanced the two-electron oxygen reduction to increase H2O2 yields.
关键词： WO3,H2O2,Photoelectrocatalysis,Dopamine,Organic pollutant,Saline wastewater
更新于2025-09-19 17:15:36
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Determination of dopamine using the indium tin oxide electrode modified with direct electrodeposition of gold–platinum nanoparticles
摘要： Gold–platinum (Au–Pt) nanoparticles (NPs) with a ratio of 3:1 solution of chloride salts in the starting electrolyte were deposited on an indium tin oxide (ITO) surface, using a direct electrochemical method, by 40 successive cyclic voltammetry (CV) scans to obtain AuPtNPs/ITO electrode. The deposited nanoparticles were defined by energy dispersive X-ray spectroscopy (EDX) and scanning electron microscopy (SEM) and electrochemical methods. The nanoparticles size of electrodeposited was ~ 30 nm based on SEM results. The efficacy of number of CV scans in the electrodeposition of nanoparticles on the size of electrodeposited nanoparticles was tested. The elemental composition of AuPtNPs/ITO electrode was determined by EDX. Electrochemical studies proved that the electrocatalytic activity of prepared electrode is excellent towards the oxidation of dopamine (DP). The concentration range of DP from 400 nM to 350 μM was linear and limit of detection DP was 20 nM. It was shown that the AuPtNPs/ITO electrode can be used as a sensor with high reproducibility, sensitivity, and long term stability. The selectivity of electrode for determination of DP was verified with investigating the effect of substances by potential interference on the response of electrode. AuPtNPs/ITO electrode was used for the determination of DP in injection and real samples, with acceptable results.
关键词： Dopamine,Gold–platinum alloy,Nanoparticles,Indium tin oxide electrode
更新于2025-09-19 17:15:36
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Fabrication of non-destructive and enhanced electrochemiluminescence interface for reusable detection of cell-released dopamine
摘要： Quantification of cell-released dopamine (DA) is essential to understand various biological processes. However, concentration of DA outside living cells may increase and decrease in a short time. Thus, approaches used to detect cell-released DA should meet higher demands. Herein, a simple and green method is employed to in situ growth of gold nanoparticles on the surface of WS2 nanosheets. The defects of prepared Au-WS2 nanocomposites may accelerate electron transfer and facilitate the absorption of dissolved oxygen. As a result, Au-WS2 nanocomposites-enhanced electrochemiluminescence (ECL) is observed for the first time, and is further used to fabricate a non-destructive and label-free analytical interface. The ECL interface can selectively detect DA in a range of 5.0 nM–200 μM with a detection limit of 3.23 nM. Meanwhile, since the architecture on the ECL interface is not destroyed during the detection procedure, DA can be quantified continuously at least six times after one fabrication. In addition, the proposed ECL interface can accurately monitor the release of DA from PC12 cells manipulated by K+ and nifidipine, indicating great potential of this ECL sensor for surveying DA-related investigations.
关键词： Cell-released dopamine,ECL interface,Au-WS2 nanocomposites,Non-destruction,Reusability
更新于2025-09-19 17:15:36
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A highly flexible and selective dopamine sensor based on Pt-Au nanoparticle-modified laser-induced graphene
摘要： A highly flexible and selective electrochemical sensor based on a Pt-Au nanoparticles (Pt-AuNPs) modified laser-induced graphene (LIG)/Polydimethylsiloxane (PDMS) electrode is presented for the detection of dopamine (DA). The Pt-AuNPs exhibited high electrocatalytic activity in response to the oxidation of DA, and the peak current of DA detected by the Pt-AuNPs/LIG/PDMS electrode linearly increased with DA concentration. The fabricated sensor also exhibited an excellent sensitivity of approximately 865.80 μA/mM cm?2 and a detection limit of 75 nM in a neutral solution. In addition, it showed high selectivity for interfering compounds such as like uric acid (UA) and ascorbic acid (AA). Clearly defined current peaks, with a separation of approximately 0.11 V, were observed for DA and UA. Finally, DA was successfully detected in human urine.
关键词： Metal nanoparticles,Laser-induced graphene,Dopamine,Flexible substrate,Electrochemical sensor
更新于2025-09-19 17:13:59