Zhi-Ling Song

Alkyne-functionalized superstable graphitic silver nanoparticles for Raman imaging.

Noble metals, especially gold, have been widely used in plasmon resonance applications. Although silver has a larger optical cross section and lower cost than gold, it has attracted much less attention because of its easy corrosion, thereby degrading plasmonic signals and limiting its applications. To circumvent this problem, we report the facile synthesis of superstable AgCu@graphene (ACG) nanoparticles (NPs). The growth of several layers of graphene onto the surface of AgCu alloy NPs effectively protects the Ag surface from contamination, even in the presence of hydrogen peroxide, hydrogen sulfide, and nitric acid. The ACG NPs have been utilized to enhance the unique Raman signals from the graphitic shell, making ACG an ideal candidate for cell labeling, rapid Raman imaging, and SERS detection. ACG is further functionalized with alkyne-polyethylene glycol, which has strong Raman vibrations in the Raman-silent region of the cell, leading to more accurate colocalization inside cells. In sum, this work provides a simple approach to fabricate corrosion-resistant, water-soluble, and graphene-protected AgCu NPs having a strong surface plasmon resonance effect suitable for sensing and imaging.

Fabrication of Graphene-isolated-Au-nanocrystal Nanostructures for Multimodal Cell Imaging and Photothermal-enhanced Chemotherapy

Using nanomaterials to develop multimodal systems has generated cutting-edge biomedical functions. Herein, we develop a simple chemical-vapor-deposition method to fabricate graphene-isolated-Au-nanocrystal (GIAN) nanostructures. A thin layer of graphene is precisely deposited on the surfaces of gold nanocrystals to enable unique capabilities. First, as surface-enhanced-Raman-scattering substrates, GIANs quench background fluorescence and reduce photocarbonization or photobleaching of analytes. Second, GIANs can be used for multimodal cell imaging by both Raman scattering and near-infrared (NIR) two-photon luminescence. Third, GIANs provide a platform for loading anticancer drugs such as doxorubicin (DOX) for therapy. Finally, their NIR absorption properties give GIANs photothermal therapeutic capability in combination with chemotherapy. Controlled release of DOX molecules from GIANs is achieved through NIR heating, significantly reducing the possibility of side effects in chemotherapy. The GIANs have high surface areas and stable thin shells, as well as unique optical and photothermal properties, making them promising nanostructures for biomedical applications.

Unimolecular Catalytic DNA Biosensor for Amplified Detection of l-Histidine via an Enzymatic Recycling Cleavage Strategy

Fluorescence catalytic beacons have emerged as a general platform for sensing applications. However, almost all such sensing systems need covalent modification of the DNAzymes with fluorophore-quencher pairs, which may require elaborate design of the synthetic routes and many heavy and complicated synthetic steps and result in increased cost and lower synthesis yield. Here we report the construction of fluorescent cascadic catalytic beacons. With separation of the molecular recognition module from the signal reporter, this new design both avoids DNAzyme modifications and improves sensitivity through an endonuclease-based cascadic enzymatic signal amplification. This allows detection of L-histidine with high sensitivity (LOD = 200 nM) and excellent specificity. The proposed sensing system has also been used for detection of L-histidine in cellular homogenate with satisfactory results.

A label-free electrochemical biosensor for highly sensitive and selective detection of DNA via a dual-amplified strategy.

In this work, by combining the enzymatic recycling reaction with the DNA functionalized gold nanoparticles (AuNPs)-based signal amplification, we have developed an electrochemical biosensor for label-free detection of DNA with high sensitivity and selectivity. In the new designed biosensor, a hairpin-structured probe HP was designed to hybridize with target DNA first, and an exonuclease ExoIII was chosen for the homogeneous enzymatic cleaving amplification. The hybridization of target DNA with the probe HP induced the partial cleavage of the probe HP by ExoIII to release the enzymatic products. The enzymatic products could then hybridize with the hairpin-structured capture probe CP modified on the electrode surface. Finally, DNA functionalized AuNPs was further employed to amplify the detection signal. Due to the capture of abundant methylene blue (MB) molecules by both the multiple DNAs modified on AuNPs surface and the hybridization product of capture DNA and enzymatic products, the designed biosensor achieved a high sensitivity for target DNA, and a detection limit of 0.6 pM was obtained. Due to the employment of two hairpin-structured probes, HP and CP, the proposed biosensor also exhibited high selectivity to target DNA. Moreover, since ExoIII does not require specific recognition sequences, the proposed biosensor might provide a universal design strategy to construct DNA biosensor which can be applied in various biological and medical samples.

Magnetic Graphitic Nanocapsules for Programmed DNA Fishing and Detection

Graphene nanomaterials are typically used in biosensing applications, and they have been demonstrated as good fluorescence quenchers. While many conventional amplification platforms are available, developing new nanomaterials and establishing simple, enzyme-free and low-cost strategies for high sensitivity biosensing is still challenging. Therefore, in this work, a core-shell magnetic graphitic nanocapsule (MGN) material is synthesized and its capabilities for the detection of biomolecules are investigated. MGN combines the unique properties of graphene and magnetic particles into one simple and sensitive biosensing platform, which quenches around 98% of the dye fluorescence within minutes. Based on a programmed multipurpose DNA capturing and releasing strategy, the MGN sensing platform demonstrates an outstanding capacity to fish, enrich, and detect DNA. Target DNA molecules as low as 50 pM could be detected, which is 3-fold lower than the limit of detection commonly achieved by carbon nanotube and graphene-based fluorescent biosensors. Moreover, the MGN platform exhibits good sensing specificity against DNA mismatch tests. Overall, therefore, these magnetic graphitic nanocapsules demonstrate a promising tool for molecular disease diagnosis and biomedicine. This simple fishing and enrichment strategy may also be extended to other biological and environmental applications and systems.

Plasma-assisted nitrogen doping of graphene-encapsulated Pt nanocrystals as efficient fuel cell catalysts

We have synthesized a nanostructure with a platinum (Pt) nanocrystal core and a few-layer graphene shell. This graphene-encapsulated Pt nanocrystal (GPN) was fabricated through a simple chemical vapor deposition (CVD) method. After investigating the electrocatalytic activities of GPNs, their ability to act as a relatively good fuel cell catalyst was confirmed. Furthermore, to further improve their catalytic activity, a plasma-assisted nitrogen doping method was developed, and the nitrogen-doped graphene-encapsulated Pt nanocrystal (N-GPN) also demonstrated efficient electroactivities, in fact much higher than those reported for conventional Pt–graphene composite catalysts due to their small particle diameter, uniform size distribution, sufficient graphene–Pt contact, and new generation of activation sites after nitrogen doping. This simple and efficient approach could also be extended to the preparation of other alloy nanocrystals coated with a graphene shell for electrocatalytic or electrochemical sensor applications.

Hollow graphitic nanocapsules as efficient electrode materials for sensitive hydrogen peroxide detection.

Carbon nanomaterials are typically used in electrochemical biosensing applications for their unique properties. We report a hollow graphitic nanocapsule (HGN) utilized as an efficient electrode material for sensitive hydrogen peroxide detection. Methylene blue (MB) molecules could be efficiently adsorbed on the HGN surfaces, and this adsorption capability remained very stable under different pH regimes. HGNs were used as three-dimensional matrices for coimmobilization of MB electron mediators and horseradish peroxidase (HRP) to build an HGN-HRP-MB reagentless amperometric sensing platform to detect hydrogen peroxide. This simple HGN-HRP-MB complex demonstrated very sensitive and selective hydrogen peroxide detection capability, as well as high reproducibility and stability. The HGNs could also be utilized as matrices for immobilization of other enzymes, proteins or small molecules and for different biomedical applications.

Quench-Shield Ratiometric Upconversion Luminescence Nanoplatform for Biosensing

Upconversion nanoparticles (UCNPs) possess several unique features, but they suffer from surface quenching effects caused by the interaction between the UCNPs and fluorophore. Thus, the use of UCNPs for target-induced emission changes for biosensing and bioimaging has been challenging. In this work, fluorophore and UCNPs are effectively separated by a silica transition layer with a thickness of about 4 nm to diminish the surface quenching effect of the UCNPs, allowing a universal and efficient luminescence resonance energy transfer (LRET) ratiometric upconversion luminescence nanoplatform for biosensing applications. A pH-sensitive fluorescein derivative and Hg(2+)-sensitive rhodamine B were chosen as fluoroionphores to construct the LRET nanoprobes. Both showed satisfactory target-triggered ratiometric upconversion luminescence responses in both solution and live cells, indicating that this strategy may find wide applications in the design of nanoprobes for various biorelated targets.

Fluorescent Nanosensor for Probing Histone Acetyltransferase Activity Based on Acetylation Protection and Magnetic Graphitic Nanocapsules

Protein acetylation catalyzed by histone acetyltransferases (HATs) is significant in biochemistry and pharmacology because of its crucial role in epigenetic gene regulations. Herein, an antibody-free fluorescent nanosensor is developed for the facile detection of HAT activity based on acetylation protection against exopeptidase cleavage and super-quenching ability of nanomaterials. It is shown for the first time that HAT-catalyzed acetylation could protect the peptide against exopeptidase digestion. FITC-tagged acetylated peptide causes the formation of a nano-quenchers/peptide nano-complex resulting in fluorescence quenching, while the unacetylated peptide is fully degraded by exopeptidase to release the fluorophore and restore fluorescence. Four kinds of nano-quenchers, including core-shell magnetic graphitic nanocapsules (MGN), graphene oxide (GO), single-walled carbon nanotubes (SWCNTs), and gold nanoparticles (AuNPs), are comprehensively compared. MGN shows the best selectivity to recognize the acetylated peptide and the lowest detection limit because of its excellent quenching efficiency and magnetic enrichment property. With this MGN-based nanosensor, HAT p300 is detected down to 0.1 nM with wide linear range from 0.5 to 100 nM. This sensor is feasible to assess HAT inhibition and detect p300 activity in cell lysate. The proposed nanosensor is simple, sensitive, and cost-effective for HAT assay, presenting a promising toolkit for epigenetic research and HAT-targeted drug discovery.

Stable and unique graphitic Raman internal standard nanocapsules for surface-enhanced Raman spectroscopy quantitative analysis

Graphitic nanomaterials have unique, strong, and stable Raman vibrations that have been widely applied in chemistry and biomedicine. However, utilizing them as internal standards (ISs) to improve the accuracy of surface-enhanced Raman spectroscopy (SERS) analysis has not been attempted. Herein, we report the design of a unique IS nanostructure consisting of a large number of gold nanoparticles (AuNPs) decorated on multilayered graphitic magnetic nanocapsules (AGNs) to quantify the analyte and eliminate the problems associated with traditional ISs. The AGNs demonstrated a unique Raman band from the graphitic component, which was localized in the Raman silent region of the biomolecules, making them an ideal IS for quantitative Raman analysis without any background interference. The IS signal from the AGNs also indicated superior stability, even under harsh conditions. With the enhancement of the decorated AuNPs, the AGN nanostructures greatly improved the quantitative accuracy of SERS, in particular the exclusion of quantitative errors resulting from collection loss and non-uniform distribution of the analytes. The AGNs were further utilized for cell staining and Raman imaging, and they showed great promise for applications in biomedicine.