Design, Synthesis, and Characterization of a Novel 2'-5'-Linked Amikacin-Binding Aptamer: An Experimental and MD Simulation Study.

To extend the approach of using RNA aptamers as transient protective groups for the synthesis of novel small-molecule drug derivatives from the existing aminoglycosides, we incorporated 2'-5' phosphodiester backbone modification in a structurally known neomycin RNA aptamer and studied the binding of a series of aminoglycosides using isothermal calorimetry (ITC) and molecular dynamics (MD) simulation. Experimental characterization of amikacin, a commercially available and widely used aminoglycoside for treating bacterial infections, shows that the aptamer A1 with a 2'-5' linkage between G15 and U16 exhibits a sevenfold increase in binding affinity with a lower binding energy compared to the native aptamer. Molecular dynamics (MD) simulation studies rationalize that this noncanonical linkage generates a narrower binding pocket by creating a superspiral RNA helical structure, which improves the ligand's fit in the binding pocket. These results provide new insights into applying 2'-5' linkages to diversify functional RNA aptamers as noncovalent protective groups in the synthesis of aminoglycoside derivatives, which can be further extended to other current drug molecules and complex natural compounds to make new pools of drug candidates more efficiently.

Fabrication of hexahedral Au-Pd/graphene nanocomposites biosensor and its application in cancer cell H2O2 detection.

Currently, real time monitoring of chemical substances in vivo and in vitro has gained enormous attraction, and many researches reports have been focused on the design and construction of high-performance biosensor devices. In this work, a high-performance sensor was constructed by taking advantage of the excellent electrochemical activity and high-index facets of Au-Pd nanocubes and the large surface of rGO. Glassy carbon electrodes (GCEs) were modified by both Au-Pd nanocubes and rGO nanocomposites via physical adsorption. Transmission electron microscopy (TEM) and X-ray diffraction (XRD) were utilized to characterize and identify this unique nanostructure. These three-dimensional nanocomposites possess a high electroactive surface area and an excellent electrical conductivity, which resulted in favorable electroreduction activity toward H2O2 with a lower detection limit of 4 nM, a wide linear range from 0.005 µM to 3.5 mM and a rapid response time. Furthermore, the proposed sensor exhibited desirable performance in the detection of endogenous H2O2 in human serum samples and real-time monitoring of H2O2 released from living breast cancer cell lines. In summary, this work not only provides a potential method to construct a physiological and pathological H2O2 biosensor but also makes a valuable contribution to the early diagnosis of different cancers.

Trimetallic AuPtPd nanocomposites platform on graphene: Applied to electrochemical detection and breast cancer diagnosis.

Recently, great efforts have been made to use biosensors for the early diagnosis of cancer. Specifically, using a biomarker to detect H2O2 in physiological conditions is of great significance for understanding the signal transduction pathways and achieving early cancer diagnosis. In this work, we report an innovative H2O2 sensor that was fabricated by trimetallic AuPtPd nanocomposites platform on reduced graphene oxide (rGO) nanosheets with the modification of the rGO and trimetallic AuPtPd nanoparticles on a glassy carbon electrode (GCE) by physical adsorption. Transmission electron microscopy (TEM) and X-ray diffraction (XRD) were utilized to characterize and identify these unique nanocomposites. In addition, the electrochemical properties of the proposed sensor were evaluated by cyclic voltammetry and chronoamperometry. Electrochemical research has demonstrated that the AuPtPd/rGO-modified GCE showed excellent electrocatalytic activity towards the reduction of H2O2, including a wider linear range from 0.005 µM to 6.5 mM, a low detection limit of 2 nM, good selectivity and acceptable repeatability. Moreover, the sensor can monitor the release of H2O2 release from living cancer cells. Therefore, this study not only improves simplicity, sensitivity and quantitatively for detection H2O2 in cells at nM level but also provides a foundation for the biological and biomedical applications such as the early diagnosis of cancer.

Preparation of Nano Au and Pt Alloy Microspheres Decorated with Reduced Graphene Oxide for Nonenzymatic Hydrogen Peroxide Sensing.

The flourish of nanotechnology has brought new vitality to the research and development of electrochemical sensing materials. In this work, we successfully synthesized Nano Au and Pt alloy microspheres decorated with reduced graphene oxide (RGO/nAPAMSs) by a simple, facile, and eco-friendly one-step reduction strategy for the fabrication of highly sensitive nonenzymatic H2O2 sensing interfaces. Energy-dispersive X-ray spectroscopy mapping (EDX mapping), energy-dispersive X-ray spectroscopy analysis (EDX), transmission electron microscopy (TEM), Fourier transform infrared spectrum (FT-IR), and X-ray diffraction spectrum (XRD) were employed to characterize RGO/nAPAMSs from a microscopic perspective. The results of cyclic voltammetry and chronoamperometry exhibited excellent electrochemical behaviors toward H2O2, with a rapid response time within 5 s, remarkable sensitivity of 1117.0 µA mM-1 cm-2, wide linear range of 0.005 to 4.0 mM and lower detection limit of 0.008 µM (S/N = 3), which provide RGO/nAPAMS not only a promising prospect for the quantitative detection of H2O2 but also a potential application in other fields of sensors. Moreover, further analysis showed the principles of the superior H2O2 sensing performance of RGO/nAPAMSs. This discovery provides a significant contribution to future study in nonenzymatic H2O2 sensing based on Nano Pt, Nano Au noble metal electrocatalysts.

Synthesis of tetrahexahedral Au-Pd core-shell nanocrystals and reduction of graphene oxide for the electrochemical detection of epinephrine.

An innovative epinephrine sensor was fabricated by integrating tetrahexahedral (THH) Au-Pd core-shell nanocrystals on reduced graphene oxide (rGO) nanosheets. Furthermore, the nanocomposites combined the large specific areas of rGO with the high-index facets and excellent electrocatalytic activity of the THH Au-Pd nanocrystals, and the nanocomposites were an essential adapter for detecting epinephrine. In the present work, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) were used to identify and characterize these unique nanocomposites, and the results revealed that a unique THH Au-Pd/rGO core-shell nanostructure was synthesized successfully. To further explore the electrochemical behaviors of these nanomaterials at a GC electrode, we applied cyclic voltammetry (CV), differential pulse voltammetry (DPV) and amperometry to study the conductivity and electrocatalytic activity of the proposed sensor, and the results suggested that the sensor based on Au-Pd/rGO presented a lower limit of detection (0.0012 µM at a signal to noise ratio of 3), wide linear detection range (0.001 µM to 1000 µM), and extraordinary selectivity and reproducibility. Moreover, the data showed that the sensor possessed good stability and acceptable accuracy to detect epinephrine in human serum samples. In summary, this work is not only a potential way to manufacture various nonenzymatic sensors but also a significant contribution to further studies in catalysis, cell fuel cells and other relevant applications.

Synthesis of Pb nanowires-Au nanoparticles nanostructure decorated with reduced graphene oxide for electrochemical sensing.

Graphene sheets are a sp2-hybridized carbon material that offer extraordinary electrical conductivity and excellent thermal and mechanical properties. They are expected to find use in a wide variety of applications. In this study, a new novel electrocatalyst, a Pb nanowires-Au nanoparticles nanocomposite decorated with reduced graphene oxide (rGO-Pb NWs-Au NPs), was successfully synthesized by an effective and simple approach. Transmission electron microscopy (TEM), X-ray diffraction (XRD) and Raman spectroscopy were employed to observe the as-prepared nanomaterial. In addition, the electrochemical behaviors of a rGO-Pb NWs-Au NPs-modified glassy carbon (GC) electrode were evaluated by cyclic voltammetry and chronoamperometry. The final prepared sensor exhibited favorable electroreduction activity towards H2O2 with a remarkable sensitivity of 552.43µAmM-1cm-2, a wide linear range of 0.005-1.25mM, a detection limit of 0.6µM and a rapid response time (within 5s). Moreover, the sensor also exhibited good reproducibility, selectivity and stability. Therefore, the present work also provides a potential practicable approach to fabricate various of non-enzymatic amperometric sensors, such as sensors for the detection of glucose, urea, ascorbic acid and dopamine.