Yuxiu Zou

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.

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.

Modulating the Morphology of Gold Graphitic Nanocapsules for Plasmon Resonance-Enhanced Multimodal Imaging

With their unique optical properties and distinct Raman signatures, graphitic nanomaterials can serve as substrates for surface-enhanced Raman spectroscopy (SERS) or provide signal amplification for bioanalysis and detection. However, a relatively weak Raman signal has limited further biomedical applications. This has been addressed by encapsulating gold nanorods (AuNRs) in a thin graphitic shell to form gold graphitic nanocapsules. This step improves plasmon resonance, which enhances Raman intensity, and has the potential for integrating two-photon luminescence (TPL) imaging capability. However, changing the morphology of gold graphitic nanocapsules such that high quality and stability are achieved remains a challenge. To address this task, we herein report a confinement chemical vapor deposition (CVD) method to prepare the construction of AuNR-encapsulated graphitic nanocapsules with these properties. Specifically, through morphological modulation, we (1) achieved higher plasmon resonance with near-IR incident light, thus achieving greater Raman intensity, and (2) successfully integrated two-photon luminescence dual-modal (Raman/TPL) bioimaging capabilities. Cancer-cell-specific aptamers were further modified on the AuNR@G graphitic surface through simple, but strong, π-π interactions to achieve imaging selectivity through differential cancer cell recognition.

Simultaneous Application of Photothermal Therapy and an Anti‐inflammatory Prodrug using Pyrene–Aspirin‐Loaded Gold Nanorod Graphitic Nanocapsules

Photothermal therapy (PTT) has been extensively developed as an effective approach against cancer. However, PTT can trigger inflammatory responses, in turn simulating tumor regeneration and hindering subsequent therapy. A therapeutic strategy was developed to deliver enhanced PTT and simultaneously inhibit PTT-induced inflammatory response. 1-Pyrene methanol was utilize to synthesize the anti-inflammatory prodrug pyrene-aspirin (P-aspirin) with a cleavable ester bond and also facilitate loading the prodrug on gold nanorod (AuNR)-encapsulated graphitic nanocapsule (AuNR@G), a photothermal agent, through π-π interactions. Such AuNR@G-P-aspirin complexes were used for near-infrared laser-triggered photothermal ablation of solid tumor and simultaneous inhibition of PTT-induced inflammation through the release of aspirin in tumor milieu. This strategy showed excellent effects in vitro and in vivo.

In situ targeted MRI detection of Helicobacter pylori with stable magnetic graphitic nanocapsules

Helicobacter pylori infection is implicated in the aetiology of many diseases. Despite numerous studies, a painless, fast and direct method for the in situ detection of H. pylori remains a challenge, mainly due to the strong acidic/enzymatic environment of the gastric mucosa. Herein, we report the use of stable magnetic graphitic nanocapsules (MGNs), for in situ targeted magnetic resonance imaging (MRI) detection of H. pylori. Several layers of graphene as the shell effectively protect the magnetic core from corrosion while retaining the superior contrast effect for MRI in the gastric environment. Boronic-polyethylene glycol molecules were synthesized and modified on the MGN surface for targeted MRI detection. In a mouse model of H. pylori-induced infection, H. pylori was specifically detected through both T2-weighted MR imaging and Raman gastric mucosa imaging using functionalized MGNs. These results indicated that enhancement of MRI using MGNs may be a promising diagnostic and bioimaging platform for very harsh conditions.

Surfactant-free interface suspended gold graphitic SERS substrate for simultaneous multiphase analysis

Simultaneous multiphase detection of multiplex analytes is important, albeit challenging, especially in pharmaceuticals analysis since drugs with lipid and water solubility were often administrated together for synergistic therapy. Surface-enhanced Raman spectroscopy (SERS) is a label-free and sensitive tool for multiplex analytes detection at multiphase interfaces. However, the requirements of inducers or surfactant surface modification of the SERS substrate have restricted extensive applications. Herein, we developed a graphene-isolated-Au-nanocrystal based multiphase analysis system. Unexpectedly, the gold graphitic SERS substrate can simply suspend at the interface of the different phase without the involvement of any surfactant. Therefore, the proximity of substrate with analyte molecules remains unaffected. Such suspended substrate not only ensures sensitive SERS detection but also enables the enrichment of analytes from the different phase simultaneously without interference. Moreover, the graphitic shell of the SERS substrate has a unique vibration band located in the Raman biological silence region which is utilized as the internal standard and improves the SERS quantification accuracy. Efficient ex vivo multiphase enrichment and detection of mimic lipid- and water-soluble drugs injected into mice were demonstrated with such gold graphitic substrate, showing the potential of this simultaneous multiplex pharmacokinetic analysis.

Portable and Label-free Detection of Blood Bilirubin with Graphene-isolated-Au-nanocrystals Paper Strip

Point-of-care testing (POCT) devices represent a growing field that aims to develop low-cost, rapid, sensitive diagnostic testing platforms that are portable and self-contained. Surface-enhanced Raman spectroscopy (SERS) is an approach has shown high potential in POCT technology. However, the specificity or ability to uniquely detect a desired biomarker in complex biological samples is a key factor for translating SERS technologies to POCT. Herein, we fabricated cellulose SERS strips (CS) decorated with novel plasmonic nanoparticles, termed graphene-isolated-Au-nanocrystals (GIANs), for the portable detection of complex biological samples. This CS@GIANs SERS strip was used to detect free bilirubin (BR) in the blood of newborns, a biomarker of jaundice, without sample labeling or prepreparation. CS@GIANs showed superior affinity to hydrophobic BR molecules compared to typical SERS substrate, which reduced the steric hindrance effect from the nonspecific binding of BR with serum albumin in blood and improved sensitivity. Meanwhile, with the separation property of cellulose chromatography papers, CS@GIANs showed superior anti-interference to other biomolecules that had been previously adsorbed on the SERS strip. Moreover, the SERS signal from the graphitic shell of GIANs could be used as a stable internal calibration standard, which improved the reproducibility and accuracy of Raman analysis. Such a cellulose SERS strip holds high potential for enhancing current efforts in the development of rapid and low-cost point-of-care diagnostic testing.

Corrigendum: In situ targeted MRI detection of Helicobacter pylori with stable magnetic graphitic nanocapsules

This corrects the article DOI: 10.1038/ncomms15653.