Apt-Conjugated PDMS-ZnO/Ag-Based Multifunctional Integrated Superhydrophobic Biosensor with High SERS Activity and Photocatalytic Sterilization Performance.

Sensitive detection and efficient inactivation of pathogenic bacteria are crucial for halting the spread and reproduction of foodborne pathogenic bacteria. Herein, a novel Apt-modified PDMS-ZnO/Ag multifunctional biosensor has been developed for high-sensitivity surface-enhanced Raman scattering (SERS) detection along with photocatalytic sterilization towards Salmonella typhimurium (S. typhimurium). The distribution of the electric field in PDMS-ZnO/Ag with different Ag sputtering times was analyzed using a finite-difference time-domain (FDTD) algorithm. Due to the combined effect of electromagnetic enhancement and chemical enhancement, PDMS-ZnO/Ag exhibited outstanding SERS sensitivity. The limit of detection (LOD) for 4-MBA on the optimal SERS substrate (PZA-40) could be as little as 10-9 M. After PZA-40 was modified with the aptamer, the LOD of the PZA-40-Apt biosensor for detecting S. typhimurium was only 10 cfu/mL. Additionally, the PZA-40-Apt biosensor could effectively inactivate S. typhimurium under visible light irradiation within 10 min, with a bacterial lethality rate (Lb) of up to 97%. In particular, the PZA-40-Apt biosensor could identify S. typhimurium in food samples in addition to having minimal cytotoxicity and powerful biocompatibility. This work provides a multifunctional nanoplatform with broad prospects for selective SERS detection and photocatalytic sterilization of pathogenic bacteria.

Synthesis and Characterization of Magnetoplasmonic Air-Stable Au@FeCo.

The synthesis of FeCo alloys as highly magnetic nanoparticles has been valuable, as far as applications for magnetic nanoparticles are concerned. However, recently, a field of magnetoplasmonics in which magnetic nanoparticles such as the FeCo alloys doped with plasmonic materials such as Au and Ag to create a hybrid nanostructure with both properties has emerged. These magnetoplasmonic metamaterials have greatly enhanced the limit of detection of analytes in spectroscopic methods, as well as providing a more widely applicable nanoparticle to broaden the use of FeCo alloys even further. Herein, we discuss the synthesis of high-yield and fairly monodisperse spherical FeCo and Au-doped FeCo (Au@FeCo) with varying compositions of Au synthesized via the thermal decomposition of iron pentacarbonyl (Fe(CO)5) and dicobalt octacarbonyl (Co2(CO)8), followed by the addition of Au atoms using triphenylphosphine gold(I) chloride ((Ph3P)AuCl) via both coprecipitation and by delayed addition methods. The products were separated using a hand-held magnet, and then characterized via ultraviolet-visible light (UV-vis), scanning electron microscopy coupled with energy-dispersive X-ray analysis (SEM-EDX), high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), flame atomic absorption spectrometry (F-AAS), and magnetization measurements. Optical studies revealed a plasmonic peak at 550 nm in the Au@FeCo nanoparticles that had a gold content (%Au) of >2% (by weight), determined using F-AAS. Colocation of the Fe, Co, and Au were demonstrated through EDX analysis. Location of the Au atoms in the core were seen through high-resolution bright-field imaging. To understand the use of these nanoparticles for potential application in therapeutics and/or electronics, resistance measurements were performed to assess power loss as a function of frequency. We also achieved magnetization values as high as 150 emu/g and as low as 50 emu/g for gold-loaded samples based on %Au by weight. This paves the way to continue to develop magneto-plasmonic structures chemically using these synthesis strategies.

Magnetic-Core-Shell-Satellite Fe3O4-Au@Ag@(Au@Ag) Nanocomposites for Determination of Trace Bisphenol A Based on Surface-Enhanced Resonance Raman Scattering (SERRS).

As a typical representative of endocrine-disrupting chemicals (EDCs), bisphenol A (BPA) is a common persistent organic pollutant in the environment that can induce various diseases even at low concentrations. Herein, the magnetic Fe3O4-Au@Ag@(Au@Ag) nanocomposites (CSSN NCs) have been prepared by self-assembly method and applied for ultra-sensitive surface-enhanced resonance Raman scattering (SERRS) detection of BPA. A simple and rapid coupling reaction of Pauly's reagents and BPA not only solved the problem of poor affinity between BPA and noble metals, but also provided the SERRS activity of BPA azo products. The distribution of hot spots and the influence of incremental introduction of noble metals on the performance of SERRS were analyzed by a finite-difference time-domain (FDTD) algorithm. The abundance of hot spots generated by core-shell-satellite structure and outstanding SERRS performance of Au@Ag nanocrystals were responsible for excellent SERRS sensitivity of CSSN NCs in the results. The limit of detection (LOD) of CSSN NCs for BPA azo products was as low as 10-10 M. In addition, the saturation magnetization (Ms) value of CSSN NCs was 53.6 emu·g-1, which could be rapidly enriched and collected under the condition of external magnetic field. These magnetic core-shell-satellite NCs provide inspiration idea for the tailored design of ultra-sensitive SERRS substrates, and thus exhibit limitless application prospects in terms of pollutant detection, environmental monitoring, and food safety.

Multifunctional magnetic Fe3O4/Cu2O-Ag nanocomposites with high sensitivity for SERS detection and efficient visible light-driven photocatalytic degradation of polycyclic aromatic hydrocarbons (PAHs).

Polycyclic aromatic hydrocarbons (PAHs) with carcinogenic, teratogenic and mutagenic properties are persistent organic pollutants in the environment. Herein, the novel multifunctional Fe3O4/Cu2O-Ag nanocomposites (NCs) have been established for ultra-sensitive surface-enhanced Raman scattering (SERS) detection and visible light-driven photocatalytic degradation of PAHs. Fe3O4/Cu2O-Ag NCs with different amounts of Ag nanocrystals were synthesized, and the effect of Ag contents on SERS performance was studied by finite-difference time-domain (FDTD) algorithm. The synergistic interplay of electromagnetic and chemical enhancement was responsible for excellent SERS sensitivity of Fe3O4/Cu2O-Ag NCs. The limit of detection (LOD) of optimal SERS substrates (FCA-2 NCs) for Nap, BaP, Pyr and Ant was as low as 10-9, 10-9, 10-9 and 10-10 M, respectively. The SERS detection of PAHs in actual soil environment was also studied. Moreover, a simple SERS method was used to monitor the photocatalytic process of PAHs. The recovery and reuse of Fe3O4/Cu2O-Ag NCs were achieved through magnetic field, and the outstanding SERS and photocatalytic performance were still maintained even after eight cycles. This magnetic multifunctional NCs provide a unique idea for the integration of ultra-sensitive SERS detection and efficient photocatalytic degradation of PAHs, and thus will have more hopeful prospects in the field of environmental protection.

Self-sustainable and recyclable ternary Au@Cu2O-Ag nanocomposites: application in ultrasensitive SERS detection and highly efficient photocatalysis of organic dyes under visible light.

Ternary noble metal-semiconductor nanocomposites (NCs) with core-shell-satellite nanostructures have received widespread attention due to their outstanding performance in detecting pollutants through surface-enhanced Raman scattering (SERS) and photodegradation of organic pollutants. In this work, ternary Au@Cu2O-Ag NCs were designed and prepared by a galvanic replacement method. The effect of different amounts of Ag nanocrystals adsorbed on the surfaces of Au@Cu2O on the SERS activity was investigated based on the SERS detection of 4-mercaptobenzoic acid (4-MBA) reporter molecules. Based on electromagnetic field simulations and photoluminescence (PL) results, a possible SERS enhancement mechanism was proposed and discussed. Moreover, Au@Cu2O-Ag NCs served as SERS substrates, and highly sensitive SERS detection of malachite green (MG) with a detection limit as low as 10-9 M was achieved. In addition, Au@Cu2O-Ag NCs were recycled due to their superior self-cleaning ability and could catalyze the degradation of MG driven by visible light. This work demonstrates a wide range of possibilities for the integration of recyclable SERS detection and photodegradation of organic dyes and promotes the development of green testing techniques.

A Novel Au@Cu2O-Ag Ternary Nanocomposite with Highly Efficient Catalytic Performance: Towards Rapid Reduction of Methyl Orange Under Dark Condition.

Au@Cu2O core-shell nanocomposites (NCs) were synthesized by reducing copper nitrate on Au colloids with hydrazine. The thickness of the Cu2O shells could be varied by adjusting the molar ratios of Au: Cu. The results showed that the thickness of Cu2O shells played a crucial role in the catalytic activity of Au@Cu2O NCs under dark condition. The Au@Cu2O-Ag ternary NCs were further prepared by a simple galvanic replacement reaction method. Moreover, the surface features were revealed by TEM, XRD, XPS, and UV-Vis techniques. Compared with Au@Cu2O NCs, the ternary Au@Cu2O-Ag NCs had an excellent catalytic performance. The degradation of methyl orange (MO) catalyzed by Au@Cu2O-Ag NCs was achieved within 4 min. The mechanism study proved that the synergistic effects of Au@Cu2O-Ag NCs and sodium borohydride facilitated the degradation of MO. Hence, the designed Au@Cu2O-Ag NCs with high catalytic efficiency and good stability are expected to be the ideal environmental nanocatalysts for the degradation of dye pollutants in wastewater.

Rapid Uptake and Photodynamic Inactivation of Staphylococci by Ga(III)-Protoporphyrin IX.

Antimicrobial photodynamic therapy (aPDT) is a promising method for the topical treatment of drug-resistant staphylococcal infections and can be further improved by identifying mechanisms that increase the specificity of photosensitizer uptake by bacteria. Here we show that Ga(III)-protoporphyrin IX chloride (Ga-PpIX), a fluorescent hemin analog with previously undisclosed photosensitizing properties, can be taken up within seconds by Staphylococcus aureus including multidrug-resistant strains such as MRSA. The uptake of Ga-PpIX by staphylococci is likely diffusion-limited and is attributed to the expression of high-affinity cell-surface hemin receptors (CSHRs), namely iron-regulated surface determinant (Isd) proteins. A structure-activity study reveals the ionic character of both the heme center and propionyl groups to be important for uptake specificity. Ga-PpIX was evaluated as a photosensitizer against S. aureus and several clinical isolates of MRSA using a visible light source, with antimicrobial activity at 0.03 µM with 10 s of irradiation by a 405 nm diode array (1.4 J/cm2); antimicrobial activity could also be achieved within minutes using a compact fluorescent lightbulb. GaPpIX was not only many times more potent than PpIX, a standard photosensitizer featured in clinical aPDI, but also demonstrated low cytotoxicity against HEK293 cells and human keratinocytes. Ga-PpIX uptake was screened against a diverse panel of bacterial pathogens using a fluorescence-based imaging assay, which revealed rapid uptake by several Gram-positive species known to express CSHRs, suggesting future candidates for targeted aPDT.

Individually Dispersed Gold Nanoshell-Bearing Cellulose Nanocrystals with Tailorable Plasmon Resonance.

Cellulose nanocrystals (CNCs) can be attractive templates for the generation of functional inorganic/organic nanoparticles, given their fine sizes, aspect ratios, and sustainable worldwide availability in abundant quantities. Here, we present for the first time a scalable, surfactant-free, tailorable wet chemical process for converting commercially available CNCs into individual aspected gold nanoshell-bearing particles with tunable surface plasmon resonance bands. Using a rational cellulose functionalization approach, stable suspensions of positively charged CNCs have been generated. Continuous, conductive, nanocrystalline gold coatings were then applied to the individual, electrostatically stabilized CNCs via decoration with 1-3 nm diameter gold particles followed by electroless gold deposition. Optical analyses indicated that these core-shell nanoparticles exhibited two surface plasmon absorbance bands, with one located in the visible range (near 550 nm) and the other at near infrared (NIR) wavelengths. The NIR band possessed a peak maximum wavelength that could be tuned over a wide range (1000-1300 nm) by adjusting the gold coating thickness. The bandwidth and wavelength of the peak maximum of the NIR band were also sensitive to the particle size distribution and could be further refined by fractionation using viscosity gradient centrifugation.

Dry Etching with Nanoparticles: Formation of High Aspect-Ratio Pores and Channels Using Magnetic Gold Nanoclusters.

Methods for generating nanopores in substrates typically involve one or more wet-etching steps. Here a fundamentally different approach to produce nanopores in sheet substrates under dry, ambient conditions, using nanosecond-pulsed laser irradiation and magnetic gold nanoclusters (MGNCs) as the etching agents is described. Thermoplastic films (50-75 µm thickness) are coated with MGNCs then exposed to laser pulses with a coaxial magnetic field gradient, resulting in high-aspect ratio channels with tapered cross sections as characterized by confocal fluorescence tomography. The dry-etching process is applicable to a wide variety of substrates ranging from fluoropolymers to borosilicate glass, with etch rates in excess of 1 µm s-1 . Finite-element modeling suggests that the absorption of laser pulses by MGNCs can produce temperature spikes of nearly 1000 °C, which is sufficient for generating photoacoustic responses that can drive particles into the medium, guided by magnetomotive force.

Eco-friendly (green) synthesis of magnetically active gold nanoclusters.

Au-FexOy composite nanoparticles (NPs) are of great technological interest due to their combined optical and magnetic properties. However, typical syntheses are neither simple nor ecologically friendly, creating a challenging situation for process scale-up. Here we describe conditions for preparing Au-FexOy NPs in aqueous solutions and at ambient temperatures, without resorting to solvents or amphiphilic surfactants with poor sustainability profiles. These magnetic gold nanoclusters (MGNCs) are prepared in practical yields with average sizes slightly below 100 nm, and surface plasmon resonances that extend to near-infrared wavelengths, and sufficient magnetic moment (up to 6 emu g-1) to permit collection within minutes by handheld magnets. The MGNCs also produce significant photoluminescence when excited at 488 nm. Energy dispersive X-ray (EDX) analysis indicates a relatively even distribution of Fe within the MGNCs, as opposed to a central magnetic core.

Polymer-iron oxide composite nanoparticles for EPR-independent drug delivery.

Nanoparticle (NP)-based approaches to cancer drug delivery are challenged by the heterogeneity of the enhanced permeability and retention (EPR) effect in tumors and the premature attrition of payload from drug carriers during circulation. Here we show that such challenges can be overcome by a magnetophoretic approach to accelerate NP delivery to tumors. Payload-bearing poly(lactic-co-glycolic acid) NPs were converted into polymer-iron-oxide nanocomposites (PINCs) by attaching colloidal Fe3O4 onto the surface, via a simple surface modification method using dopamine polymerization. PINCs formed stable dispersions in serum-supplemented medium and responded quickly to magnetic field gradients above 1 kG/cm. Under the field gradients, PINCs were rapidly transported across physical barriers and into cells and captured under flow conditions similar to those encountered in postcapillary venules, increasing the local concentration by nearly three orders of magnitude. In vivo magnetophoretic delivery enabled PINCs to accumulate in poorly vascularized subcutaneous SKOV3 xenografts that did not support the EPR effect. In vivo magnetic resonance imaging, ex vivo fluorescence imaging, and tissue histology all confirmed that the uptake of PINCs was higher in tumors exposed to magnetic field gradients, relative to negative controls.

Time-Resolved Proteomic Visualization of Dendrimer Cellular Entry and Trafficking.

Our understanding of the complex cell entry pathways would greatly benefit from a comprehensive characterization of key proteins involved in this dynamic process. Here we devise a novel proteomic strategy named TITAN (Tracing Internalization and TrAfficking of Nanomaterials) to reveal real-time protein-dendrimer interactions using a systems biology approach. Dendrimers functionalized with photoreactive cross-linkers were internalized by HeLa cells and irradiated at set time intervals, then isolated and subjected to quantitative proteomics. In total, 809 interacting proteins cross-linked with dendrimers were determined by TITAN in a detailed temporal manner during dendrimer internalization, traceable to at least two major endocytic mechanisms, clathrin-mediated and caveolar/raft-mediated endocytosis. The direct involvement of the two pathways was further established by the inhibitory effect of dynasore on dendrimer uptake and changes in temporal profiles of key proteins.

Trace detection of tetrabromobisphenol A by SERS with DMAP-modified magnetic gold nanoclusters.

Magnetic gold nanoclusters (MGNCs) functionalized with 4-dimethylaminopyridine (DMAP) enables the trace detection of tetrabromobisphenol A (TBBPA), an environmental pollutant, using surface-enhanced Raman scattering (SERS) spectroscopy. The synthesis, cleansing, and functionalization of MGNCs are conducted in aqueous solutions; SERS samples are prepared by magnetic precipitation in the presence of trace analyte. The limit of detection (LOD) for TBBPA is greatly increased by the use of DMAP as a reporter molecule: DMAP-modified MGNCs can detect TBBPA at 10 pM in water, whereas the LOD for TBBPA by unfunctionalized Au is 1 nM. The reproducibility of picomolar TBBPA detection with DMAP-modified MGNCs is confirmed by two-dimensional correlation analysis. The high SERS sensitivity for TBBPA can be attributed to its capacity to modulate the Raman spectrum of adsorbed DMAP. This indirect mode of detection can also be applied toward the detection of other hydrophobic analytes, each identifiable by its characteristic SERS identity.

Citrate-stabilized gold nanorods.

Stable aqueous dispersions of citrate-stabilized gold nanorods (cit-GNRs) have been prepared in scalable fashion by surfactant exchange from cetyltrimethylammonium bromide (CTAB)-stabilized GNRs, using polystyrenesulfonate (PSS) as a detergent. The surfactant exchange process was monitored by infrared spectroscopy, surface-enhanced Raman scattering (SERS), and X-ray photoelectron spectroscopy (XPS). The latter established the quantitative displacement of CTAB (by PSS) and of PSS (by citrate). The Cit-GNRs are indefinitely stable at low ionic strength, and are conducive to further ligand exchange without loss of dispersion stability. The reliability of the surface exchange process supports the systematic analysis of ligand structure on the hydrodynamic size of GNRs, as described in a companion paper.

New cathepsin D inhibitor library utilizing hydroxyethyl isosteres with cyclic tertiary amines.

The design and synthesis of hydroxyethylamine isosteres as inhibitors of cathepsin D based on SAR data have been accomplished. A library of 96 of these hydroxyethylamine isosteres are described and many have proven to be very potent inhibitors of human cathepsin D activity as measured using a fluorometric assay technique, via peptide substrate Ac-Glu-Glu(Edans)-Lys-Pro-Ile-Cys-Phe-Phe-Arg-Leu-Gly-Lys(Methyl Red)-Glu-NH(2). Compounds showing strongest inhibition of cathepsin D activity were those that contain a hydroxyethyl-N'-2- or N'-(4-chlorophenyl)piperazine moiety (IC(50) values range from 0.55 to 8.5 nM), with N'-(2-pyrimidyl)piperizine (IC(50) values range from 0.5 to 21.6 nM), with N-N'- L-piperazinocolinamide (IC(50) values range from 0.001 - 0.25 nM), or N-N'-L-piperazinocolin-N-methylamide (IC(50) values range from 0.015 - 7.3 nM).