Yunqing Wang

SERS Tags: Novel Optical Nanoprobes for Bioanalysis

CONTENTS 1. Introduction 1.1. Fundamental Theory of Surface-Enhanced Raman Scattering 1.2. Optical Properties of SERS Tags 2. Synthesis of SERS Tags 2.1. Noble Metal Nanosubstrates 2.1.1. Single Particle-Based SERS Substrates 2.1.2. Nanoparticle Cluster-Based Substrates 2.2. Raman Reporter Molecules 2.2.1. Selection Principles and Reporter Types 2.2.2. Self-Assembled Monolayer Coverage Strategy 2.3. Surface Coating for Protection 2.3.1. Biomolecule Coating 2.3.2. Polymer Coating 2.3.3. Liposome Coating 2.3.4. Silica Coating 2.4. Attachment of Targeting Molecules 3. Bioanalysis Applications 3.1. Ionic and Molecular Detection 3.2. Pathogen Detection 3.3. Live-Cell Imaging 3.3.1. Cancer Marker Detection 3.3.2. Intercellular Microenvironment Sensing 3.4. Tissue SERS Imaging 3.5. In Vivo SERS Imaging 4. Challenges and Perspectives 4.1. Reproducible Signal of SERS Tags 4.1.1. Precisely Controlled Hot Spots for Nanosubstrates 4.1.2. Calibration of SERS Intensities and Enhancements 4.2. Improving Multiplexing Capability 4.3. Reduced Size for Subcellular Imaging 4.4. Development of Multifunctional Nanoplatforms 4.4.1. Magnetic SERS Dots 4.4.2. Multimodal Imaging Dots 4.4.3. SERS Tag-Based Therapeutic Systems 4.5. Biocompatibility 5. Conclusions and Remarks

Quantum dots, lighting up the research and development of nanomedicine

UNLABELLED Quantum dots (QDs) have proven themselves as powerful inorganic fluorescent probes, especially for long term, multiplexed imaging and detection. The newly developed QDs labeling techniques have facilitated the study of drug delivery on the level of living cells and small animals. Moreover, based on QDs and fluorescence imaging system, multifunctional nanocomplex integrated targeting, imaging and therapeutic functionalities have become effective materials for synchronous cancer diagnosis and treatment. In this review, we will summarize the recent advances of QDs in the research of drug delivery system from the following aspects: surface modification strategies of QDs for drug delivery, QDs as drug nanocarriers, QD-labeled drug nanocarriers, QD-based fluorescence resonance energy transfer (FRET) technique for drug release study as well as the development of multifunctional nanomedicines. Possible perspective in this field will also be discussed. FROM THE CLINICAL EDITOR This review discusses the role and significance of quantum dots (QDs) from the following aspects: surface modification strategies of QDs for drug delivery, QDs as drug nanocarriers, QD-labeled drug nanocarriers, QD-based fluorescence resonance energy transfer (FRET) technique for drug release study as well as the development of multifunctional nanomedicines.

Nanomaterial-assisted aptamers for optical sensing.

Aptamers are single-strand DNA or RNA selected in vitro that bind specifically with a broad range of targets from metal ions, organic molecules, to proteins, cells and microorganisms. As an emerging class of recognition elements, aptamers offer remarkable convenience in the design and modification of their structures, which has motivated them to generate a great variety of aptamer sensors (aptasensors) that exhibit high sensitivity as well as specificity. On the other hand, the development of nanoscience and nanotechnology has generated nanomaterials with novel properties compared with their counterparts in macroscale. By integrating their strengths of both fields, recently, versatile aptamers coupling with novel nanomaterials for designing nanomaterial-assisted aptasensors (NAAs) make the combinations universal strategies for sensitive optical sensing. NAAs have been considered as an excellent sensing platform and found wide applications in analytical community. In this review, we summarize recent advances in the development of various optical NAAs, employing various detection techniques including colorimetry, fluorometry, surface-enhanced Raman scattering (SERS), magnetic resonance imaging (MRI) and surface plasmon resonance (SPR).

Highly Sensitive SERS Detection of As3+ Ions in Aqueous Media using Glutathione Functionalized Silver Nanoparticles

A highly sensitive surface-enhanced Raman scattering (SERS) platform for the selective trace analysis of As(3+) ions was reported based on glutathione (GSH)/4-mercaptopyridine (4-MPY)-modified silver nanoparticles (AgNPs). Here, GSH conjugated on the surface of AgNPs for specifical binding with As(3+) ions in aqueous solution through As-O linkage and 4-MPY was used as a Raman reporter. When As(3+) ions were added to the system, the binding of As(3+) with GSH resulted in the aggregation of AgNPs, and excellent Raman signal of 4-MPY reporters was obtained which can reflect the concentration of As(3+) indirectly. Under optimal assay conditions, the limit of detection (LOD) was estimated to be as low as 0.76 ppb, which is lower than the WHO defined limit (10 ppb), and an excellent linear range of 4-300 ppb was obtained. The practical application had been carried out for determination of As(3+) in real water samples.

Colorimetric Detection of Trace Copper Ions Based on Catalytic Leaching of Silver-Coated Gold Nanoparticles

A colorimetric, label-free, and nonaggregation-based silver coated gold nanoparticles (Ag/Au NPs) probe has been developed for detection of trace Cu(2+) in aqueous solution, based on the fact that Cu(2+) can accelerate the leaching rate of Ag/Au NPs by thiosulfate (S(2)O(3)(2-)). The leaching of Ag/Au NPs would lead to dramatic decrease in the surface plasmon resonance (SPR) absorption as the size of Ag/Au NPs decreased. This colorimetric strategy based on size-dependence of nanoparticles during their leaching process provided a highly sensitive (1.0 nM) and selective detection toward Cu(2+), with a wide linear detection range (5-800 nM) over nearly 3 orders of magnitude. The cost-effective probe allows rapid and sensitive detection of trace Cu(2+) ions in water samples, indicating its potential applicability for the determination of copper in real samples.

Cadmium telluride quantum dots as pH-sensitive probes for tiopronin determination

The pH-sensitive cadmium telluride (CdTe) quantum dots (QDs) were used as proton probes for tiopronin determination. Based on the fluorescence quenching of CdTe QDs caused by tiopronin, a simple, rapid and specific quantitative method was proposed. Under the optimal conditions, the calibration plot of ln(F(0)/F) with concentration of tiopronin was linear in the range of 0.15-20 microg mL(-1)(0.92-122.5 micromol L(-1)) with correlation coefficient of 0.998. The limit of detection (LOD) (3sigma/k) was 0.15 microg mL(-1)(0.92 micromol mL(-1)). The content of tiopronin in pharmaceutical tablet was determined by the proposed method and the result agreed with that obtained from the oxidation-reduction titration method and the claimed value.

Sensitive Near-Infrared Fluorescent Probes for Thiols Based on Se-N Bond Cleavage: Imaging in Living Cells and Tissues

Cy-NiSe and Cy-TfSe were designed and synthesized as sensitive near-infrared (NIR) fluorescent probes for detecting thiols on the basis of Se-N bond cleavage both in cells and in tissues. Since a donor-excited photoinduced electron transfer (d-PET) process occurs between the modulator and the fluorophore, Cy-NiSe and Cy-TfSe have weak fluorescence. On titration with glutathione, the free dye exhibits significant fluorescence enhancement. The two probes are sensitive and selective for thiols over other relevant biological species. They can function rapidly at pH 7.4, and their emission lies in the NIR region. Confocal imaging confirms that Cy-NiSe and Cy-TfSe can be used for detecting thiols in living cells and tissues.

Biocompatible Triplex Ag@SiO2@mTiO2 Core–Shell Nanoparticles for Simultaneous Fluorescence-SERS Bimodal Imaging and Drug Delivery

Herein, we report the synthesis of biocompatible triplex Ag@SiO(2)@mTiO(2) core-shell nanoparticles (NPs) for simultaneous fluorescence-surface-enhanced Raman scattering (F-SERS) bimodal imaging and drug delivery. Stable Raman signals were created by typical SERS tags that were composed of Ag NPs for optical enhancement, a reporter molecule of 4-mercaptopyridine (4-Mpy) for a spectroscopic signature, and a silica shell for protection. A further coating of mesoporous titania (mTiO(2)) on the SERS tags offered high loading capacity for a fluorescence dye (flavin mononucleotide) and an anti-cancer drug (doxorubicin (DOX)), thereby endowing the material with fluorescence-imaging and therapeutic functions. The as-prepared F-SERS dots exhibited strong fluorescence when excited by light at 460 nm whilst a stable, characteristic 4-Mpy SERS signal was detected when the excitation wavelength was changed to longer wavelength (632.8 nm), both in solution and after incorporation inside living cells. Their excellent biocompatibility was demonstrated by low cytotoxicity against MCF-7 cells, even at a high concentration of 100 μg  mL(-1). In vitro cell cytotoxicity confirmed that DOX-loaded F-SERS dots had a comparable or even greater therapeutic effect compared with the free drug, owing to the increased cell-uptake, which was attributed to the possible endocytosis mechanism of the NPs. To the best of our knowledge, this is the first proof-of-concept investigation on a multifunctional nanomedicine that possessed a combined capacity for fast and multiplexed F-SERS labeling as well as drug-loading for cancer therapy.

Upconversion Fluorescence-SERS Dual-Mode Tags for Cellular and in Vivo Imaging

Fluorescent-surface enhanced Raman scattering (F-SERS) dual mode tags showed great potential for bioimaging due to the combined advantages of intuitive, fast imaging of fluorescence and multiplex capability of SERS technique. In previously reported F-SERS tags, organic fluorescent dyes or quantum dots were generally selected to generate fluorescence signal. Herein, we reported the first proof-of-concept upconversion fluorescence (UCF)-SERS dual mode tags based on near infrared (NIR) laser (980 nm) excited upconversion nanoparticles (UCNPs) for live-cell and in vivo imaging. Three components involved in this tag: NaYF4:Yb,Er UCNPs@SiO2 serving as the fluorescent core of the tag; silver nanoparticles in situ grown on the surface of UCNPs@SiO2 for generating characteristic Raman signal; and denatured BSA coating rendering the tags stability and biocompatibility. The UCF-SERS tags integrated the NIR imaging capability of both fluorescent UCNPs and plasmonic SERS nanoprobe, which facilitated dual mode bioimaging investigation, especially for living animals. Ex vivo experiments revealed that with 980 nm and 785 nm NIR laser irradiations, the UCF and SERS signals of the tags could be detected from 3 and 7 mm deep pork tissues, respectively. Furthermore, the in vivo imaging capabilities of UCF-SERS tags were successfully demonstrated on living mice. The developed dual modality tags held great potential for medical diagnostics and therapy.

Brushing, a simple way to fabricate SERS active paper substrates

A simple and facile method has been demonstrated to fabricate low-cost surface enhanced Raman scattering (SERS) active microfluidic paper chips using a painting brush. This strategy solves the problem of mass production of highly reproducible SERS substrates without complicated or bulky micro- or nanofabrication instruments. Rhodamine 6G (R6G) was chosen as a probe molecule to evaluate the performance of the SERS active chip. To further demonstrate the possibility of this methods potential application in environmental monitoring, trace malachite green (MG) was successfully analyzed on this chip. The performance of our chips was desirable. The paper substrates with silver nanoparticles deposited by brush were found to be cost-efficient and highly sensitive (LOD for R6G and MG are 1 nM and 10 nM, respectively), and have good reproducibility (∼15% relative standard deviation).