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ABSTRACT: The detection of inflammatory changes is a key aim for the early diagnosis and treatment of several autoimmune, infectious, and metastatic diseases. While surface-enhanced Raman scattering (SERS) has the capability to provide noninvasive, in vivo imaging at sufficient depth to achieve this goal, this approach has not been exploited in the study of inflammation. SERS-active nanoparticles were coded with a unique Raman signal that was protected under a wide range of conditions and stimuli. To detect early-stage inflammation, gold nanoparticle clusters containing Raman-active molecules were conjugated to intercellular adhesion molecule 1- (ICAM-1-) specific monoclonal antibodies. SERS allowed noninvasive measurement of ICAM-1 expression in vivo with twice the sensitivity of two-photon fluorescence. This is the first time SERS has been used for in vivo detection of inflammation and is a major advance in the ever-growing toolkit of approaches for use in noninvasive, next-generation in vivo imaging.
Analytical Chemistry 07/2012; 84(14):5968-75. · 5.86 Impact Factor
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ABSTRACT: Track it down: A recognized surface-enhanced Raman scattering (SERS) nanotag signal was monitored from a thin, dispersed layer of bisphosphonate-functionalized nanotags on a bone sample, through a 20 mm thick specimen of porcine muscle tissue by surface-enhanced spatial offset Raman spectroscopy (SESORS; see picture). The result demonstrates the great potential for non-invasive in vivo bisphosphonate drug tracking.
Angewandte Chemie International Edition 07/2012; 51(34):8509-11. · 13.45 Impact Factor
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ABSTRACT: DNA functionalised nanoparticle probes offer new opportunities in analyte detection. Ultrasensitive, molecularly specific targeting of analytes is possible through the use of metallic nanoparticles and their ability to generate a surface enhanced Raman scattering (SERS) response. This is leading to a new range of diagnostic clinical probes based on SERS detection. Our approaches have shown how such probes can detect specific DNA sequences by using a biomolecular recognition event to 'turn on' a SERS response through a controlled assembly process of the DNA functionalised nanoparticles. Further, we have prepared DNA aptamer functionalised SERS probes and demonstrated how introduction of a protein target can change the aggregation state of the nanoparticles in a dose-dependant manner. These approaches are being used as methods to detect biomolecules that indicate a specific disease being present with a view to improving disease management.
Faraday Discussions 01/2011; 149:291-9; discussion 333-56. · 5.00 Impact Factor
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ABSTRACT: The development of nanoscale molecular probes capable of diagnosis, characterization, and clinical treatment of disease is leading to a new generation of imaging technologies. Such probes are particularly relevant to inflammation, where the detection of subclinical, early disease states could facilitate speedier detection that could yield enhanced, tailored therapies. Nanoparticles offer robust platforms capable of sensitive detection, and early research has indicated their suitability for the detection of vascular activation and cellular recruitment at subclinical levels. This suggests that nanoparticle techniques may provide excellent biomarkers for the diagnosis and progression of inflammatory diseases with magnetic resonance imaging (MRI), fluorescent quantum dots (QDs), and surface enhanced Raman scattering (SERS) probes being just some of the new methodologies employed. Development of these techniques could lead to a range of sensitive probes capable of ultrasensitive, localized detection of inflammation. This article will discuss the merits of each approach, with a general overview to their applicability in inflammatory diseases.
TheScientificWorldJOURNAL 01/2011; 11:1300-12. · 1.66 Impact Factor
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12/2010: pages 241 - 262; , ISBN: 9783527632756
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ABSTRACT: Metallic nanoparticles can be used as basic materials for a wide variety of purposes including building blocks for nanoassemblies, substrates for enhanced spectroscopies such as fluorescence and Raman and as labels for biomolecules. In the present paper, we report how silver and gold nanoparticles can be functionalized with specific biomolecular probes to interact in a specific manner with a target molecule to provide a change in the properties of the nanoparticles which can be measured to indicate the molecular recognition event. Examples of this approach include DNA hybridization to switch on SERRS (surface-enhanced resonance Raman scattering) when a specific target sequence is present, the use of nanoparticles for in vivo SERRS imaging and the use of nanoparticles functionalized with antibodies to provide a new type of immunoassay. These examples indicate how nanoparticles can be used to provide highly sensitive and informative data from a variety of biological systems when used in combination with SERRS.
Biochemical Society Transactions 09/2009; 37(Pt 4):697-701. · 3.71 Impact Factor
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ABSTRACT: Surface enhanced Raman scattering (SERS) has been used to detect specific pterin molecules at sub-nanomolar concentrations. SERS is fast becoming a widely used technique for the sensitive and specific detection of multiple analytes. The information-rich and concentration-dependent spectra obtained from SERS make the technique ideally placed for high speed, low cost analysis of almost any analyte. Further, to show the feasibility of SERS in the detection of biologically relevant targets, a synthetic pterin analogue of the naturally occurring pterin cofactor, tetrahydrobiopterin, has been detected at a series of concentrations and the method used for the successful detection of the synthetic pterin in mouse serum. In this analysis, spectroscopic collection was optimized for water-based pteridine derivatives using two visible wavelengths of excitation (514.5 and 632.8 nm) and differing mesoscopic metal nanoparticles allowing the limits of detection to be calculated.
The Analyst 08/2009; 134(8):1561-4. · 4.23 Impact Factor
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ABSTRACT: We report the first use of a commonly used ELISA colorimetric substrate as a SERRS marker and show how it can be used for the detection of pg ml(-1) levels of human prostate specific antigen (PSA) in clinical samples. The technique is amenable over a wide range of concentrations and lends itself to future multiplexing analysis.
The Analyst 06/2009; 134(5):842-4. · 4.23 Impact Factor
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ABSTRACT: The detection of subclinical early inflammation in autoimmune diseases is an important but currently technically demanding approach to direct initial diagnosis and subsequent choice of therapy. Recent advances in imaging using NP provides the potential to detect cellular recruitment, vascular activation or leakage at a subclinically stage of disease and may provide predictive "biomarkers" of future pathogenesis. The NP used are either untargeted and taken up by phagocytic cells, or are linked to a ligand, targeting localisation to the site of inflammation. Techniques, varying from MRI and fluorescence to Raman spectroscopy are being employed. In this short review, we summarise many of the recent developments in the field of NP imaging related to inflammation.
Autoimmunity 05/2009; 42(4):368-72. · 2.47 Impact Factor
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ABSTRACT: A synthetic library of ca. 10(13) single stranded oligodeoxynucleotides, each comprising a randomized 40mer sequence and homogeneous 10mer flanking regions, was screened for binding to recombinant human 14-3-3gamma. A single aptamer, which showed similar affinities (K(D) approximately 10(-8)M) for six isoforms of the protein, has been shown to bind to undenatured 14-3-3 protein in the cerebral spinal fluid of scrapie infected sheep.
Bioorganic Chemistry 03/2008; 36(5):215-9. · 1.21 Impact Factor
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ABSTRACT: Protein-directed dynamic combinatorial chemistry (DCC) relies on reversible chemical reactions that can function under the near-physiological conditions required by the biological target. Few classes of reaction have so far proven effective at generating dynamic combinatorial libraries (DCLs) under such constraints. In this study, we establish the conjugate addition of thiols to enones as a reaction well-suited for the synthesis of dynamic combinatorial libraries (DCLs) directed by the active site of the enzyme glutathione S-transferase (GST). The reaction is fast, freely reversible at basic pH, and easily interfaced with the protein, which is a target for the design of inhibitors in cancer therapy and the treatment of parasitic diseases such as schistosomiasis. We have synthesized DCLs based on glutathione (GSH, 1) and the enone ethacrynic acid, 2a. By varying either set of components, we can choose to probe either the GSH binding region ("G site") or the adjacent hydrophobic acceptor binding region ("H site") of the GST active site. In both cases the strongest binding DCL components are identified due to molecular amplification by GST which, in the latter system, leads to the identification of two new inhibitors for the GST enzyme.
Journal of the American Chemical Society 08/2006; 128(26):8459-67. · 9.91 Impact Factor
