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With the ever-increasing use of 3D cell models toward studying bio-nano interactions and offering alternatives to traditional 2D in vitro and in vivo experiments, methods to image biological tissue in real time and with high spatial resolution have become a must. A suitable technique therefore is surface-enhanced Raman scattering (SERS)-based microscopy, which additionally features reduced photocytotoxicity and improved light penetration. However, optimization of imaging and postprocessing parameters is still required. Herein we present a method to monitor cell proliferation over time in 3D, using multifunctional 3D-printed scaffolds composed of biologically inert poly(lactic- co -glycolic acid) (PLGA) as the base material, in which fluorescent labels and SERS-active gold nanoparticles (AuNPs) can be embedded. The combination of imaging techniques allows optimization of SERS imaging parameters for cell monitoring. The scaffolds provide anchoring points for cell adhesion, so that cell growth can be observed in a suspended 3D matrix, with multiple reference points for confocal fluorescence and SERS imaging. By prelabeling cells with SERS-encoded AuNPs and fluorophores, cell proliferation and migration can be simultaneously monitored through confocal Raman and fluorescence microscopy. These scaffolds provide a simple method to follow cell dynamics in 4D, with minimal disturbance to the tissue model.

Large-scale visualization of nanoparticle kinetics is essential for optimizing drug delivery and characterizing in vivo toxicity associated with engineered nanomaterials. Real-time tracking of nanoparticulate agents across multiple murine organs is hindered with the currently available whole-body preclinical imaging systems due to limitations in contrast, sensitivity, spatial, or temporal resolution. Herein, we demonstrate rapid volumetric tracking of gold nanoagent kinetics and biodistribution in mice at a suborgan level with single-sweep volumetric optoacoustic tomography (sSVOT). The imaging system accomplishes whole-body three-dimensional scans in less than 1.8 s, further attaining a high spatial resolution of 130 μm and sub-picomolar sensitivity. We visualized the clearance dynamics of purposely synthesized gold nanorods and nanorod clusters, featuring different sizes and surface chemistries as well as their corresponding accumulation within the liver and spleen. The newly discovered capacity to image rapid whole-body kinetics down to suborgan scales opens up new avenues for the development and characterization of diagnostic and therapeutic nanoagents.

The incidence and mortality of cancer demand more innovative approaches and combination therapies to increase treatment efficacy and decrease off-target side effects. We describe a boron-rich nanoparticle composite with potential applications in both boron neutron capture therapy (BNCT) and photothermal therapy (PTT). Our strategy is based on gold nanorods (AuNRs) stabilized with polyethylene glycol and functionalized with the water-soluble complex cobalt bis (dicarbollide) ([3,3'-Co(1,2-C 2 B 9 H 11 ) 2 ] - ), commonly known as COSAN. Radiolabeling with the positron emitter copper-64 ( 64 Cu) enabled in vivo tracking using positron emission tomography imaging. 64 Cu-labeled multifunctionalized AuNRs proved to be radiochemically stable and capable of being accumulated in the tumor after intravenous administration in a mouse xenograft model of gastrointestinal cancer. The resulting multifunctional AuNRs showed high biocompatibility and the capacity to induce local heating under external stimulation and trigger cell death in heterogeneous cancer spheroids as well as the capacity to decrease cell viability under neutron irradiation in cancer cells. These results position our nanoconjugates as suitable candidates for combined BNCT/PTT therapies.

Microencapsulation of therapeutic cells has widely advanced toward the development of treatments for various diseases, in particular seeking the protection of cell transplants from immune rejection. However, several challenges in cell therapy remain due to the lack of suitable methods to monitor in vivo microcapsule tracking, microcapsule stability and/or altered cell viability and proliferation upon transplantation. We propose in this work the incorporation of contrast agents in microcapsules, which can be easily visualized by SERS imaging. By placing SERS probes in the alginate extracellular layer, a high contrast can be obtained with negligible toxicity. Specifically, we used a pH-sensitive SERS tracking probe consisting of gold nanostars encoded with a pH-sensitive Raman-active molecule, and protected by a layer of biocompatible polymer coating, grafted on the nanoparticles via electrostatic interactions. This nanomaterial is highly sensitive within the biologically relevant pH range, 5.5-7.8. We demonstrate that this SERS-based pH sensor can provide information about cell death of microencapsulated cells, in a non-invasive manner. As a result, we expect that this approach should provide a general strategy to study biological interactions at the microcapsule level.

Environmental conditions during real-world application of bimetallic core-shell nanoparticles (NPs) often include the use of elevated temperatures, which are known to cause elemental redistribution, in turn significantly altering the properties of these nanomaterials. Therefore, a thorough understanding of such processes is of great importance. The recently developed combination of fast electron tomography with in situ heating holders is a powerful approach to investigate heat-induced processes at the single NP level, with high spatial resolution in 3D. In combination with 3D finite-difference diffusion simulations, this method can be used to disclose the influence of various NP parameters on the diffusion dynamics in Au@Ag core-shell systems. A detailed study of the influence of heating on atomic diffusion and alloying for Au@Ag NPs with varying core morphology and crystallographic details is carried out. Whereas the core shape and aspect ratio of the NPs play a minor role, twin boundaries are found to have a strong influence on the elemental diffusion., (© 2021 Wiley-VCH GmbH.)

The detection of cancer biomarkers at an early stage of tumor development is vital for effective diagnosis and treatment of cancer. Current diagnostic tools can often detect cancer only when the biomarker levels are already too high, so that the tumors have spread and treatments are less effective. It is urgent therefore to develop highly sensitive assays for the detection of such biomarkers at the lowest possible concentration. In this context, we developed a sandwich immunoassay based on surface-enhanced Raman scattering (SERS) for the ultrasensitive detection of α-fetoprotein (AFP), which is typically present in human serum as a biomarker indicative of early stages of hepatocellular carcinoma. In the immunoassay design, molybdenum disulfide (MoS 2 ) modified with a monoclonal antibody was used as a capture probe for AFP. A secondary antibody linked to an SERS-encoded nanoparticle was employed as the Raman signal reporter, that is, the transducer for AFP detection. The sandwich immunocomplex "capture probe/target/SERS tag" was deposited on a silicon wafer and decorated with silver-coated gold nanocubes to increase the density of "hot spots" on the surface of the immunosensor. The developed SERS immunosensor exhibits a wide linear detection range (1 pg mL -1 to 10 ng mL -1 ) with a limit of detection as low as 0.03 pg mL -1 toward AFP with good reproducibility (RSD < 6%) and stability. These parameters demonstrate that the proposed immunosensor has the potential to be used as an analytical platform for the detection of early-stage cancer biomarkers in clinical applications.

Once introduced into the human body, nanoparticles often interact with blood proteins, which in turn undergo structural changes upon adsorption. Although protein corona formation is a widely studied phenomenon, the structure of proteins adsorbed on nanoparticles is far less understood. We propose a model to describe the interaction between human serum albumin (HSA) and nanoparticles (NPs) with arbitrary coatings. Our model takes into account the competition between protonated and unprotonated polymer ends and the curvature of the NPs. To this end, we explored the effects of surface ligands (citrate, PEG-OMe, PEG-NH2, PEG-COOH, and glycan) on gold nanoparticles (AuNPs) and the pH of the medium on structural changes in the most abundant protein in blood plasma (HSA), as well as the impact of such changes on cytotoxicity and cellular uptake. We observed a counterintuitive effect on the ζ-potential upon binding of negatively charged HSA, while circular dichroism spectroscopy at various pH values showed an unexpected pattern in the reduction of α-helix content, as a function of surface chemistry and curvature. Our model qualitatively reproduces the decrease in α-helix content, thereby offering a rationale based on particle curvature. The simulations quantitatively reproduce the charge inversion measured experimentally through the ζ-potential of the AuNPs in the presence of HSA. Finally, we found that AuNPs with adsorbed HSA display lower toxicity and slower cell uptake rates, compared to functionalized systems in the absence of protein. Our study allows examining and explaining the conformational dynamics of blood proteins triggered by NPs and corona formation, thereby opening new avenues toward designing safer NPs for drug delivery and nanomedical applications.

This work aims at learning how the size of gold nanocarriers influences the transport of DNA-alkylating antitumoral drugs. For this purpose, we devised conjugates of mercaptoethylmitomycin C (MEMC), a DNA alkylating agent, with gold nanoparticles of different sizes (2, 5, and 14 nm), and studied how size affects drug cytotoxicity, tumor penetrability, cellular uptake, and intracellular localization using two-dimensional (2D) and three-dimensional (3D) cell models. We show that only small, 2 nm, nanoparticles can transport MEMC efficiently to the cell nucleus, whereas MEMC cell uptake is much lower when delivered by these small nanoparticles than with the larger ones. 3D cellular models showed that smaller nanoparticles can transport MEMC toward deeper areas of tumor spheroids as compared to larger nanoparticles. We discuss the insights of this work toward the efficient delivery of DNA-targeting drugs.

The efficacy of drug delivery and other nanomedicine-related therapies largely relies on the ability of nanoparticles to reach the target organ. However, when nanoparticles are injected into the bloodstream, their surface is instantly modified upon interaction with blood components, principally with proteins. It is well known that a dynamic and multi-layered protein structure is formed spontaneously on the nanoparticle upon contact with physiological media, which has been termed protein corona. Although several determinant factors involved in protein corona formation have been identified from in vitro studies, specific relationships between the nanomaterial synthetic identity and its ensuing biological identity under realistic in vivo conditions remain elusive. We present here a detailed study of in vivo protein corona formation after blood circulation of anisotropic gold nanoparticles (nanorods and nanostars). Plasmonic gold nanoparticles of different shapes and sizes were coated with polyethyleneglycol, intravenously administered in CD-1 mice and subsequently recovered. The results from gel electrophoresis and mass spectrometry analysis revealed the formation of complex protein coronas, as early as 10 minutes post-injection. The total amount of protein adsorbed onto the particle surface and the protein corona composition were found to be affected by both the particle size and shape.

We present the application of surface-enhanced Raman scattering (SERS) spectroscopy for the fast, sensitive and highly specific detection of the galectin-9 (Gal-9) protein in binding buffer (mimicking natural conditions). The method involves the use of specifically designed nanotags comprising glycan-decorated gold nanoparticles encoded with 4-mercaptobenzoic acid. At fast time scales Gal-9 can be detected down to a concentration of 1.2 nM by monitoring the SERS signal of the reporter, driven by aggregation of the functionalized Au NPs tags, induced by Gal-9 recognition. We additionally demonstrate that the sensitivity and concentration working range of the sensor can be tuned via control of aggregation dynamics and cluster size distribution.

The design of compact nanoprobes for multimodal bioimaging is a current challenge and may have a major impact on diagnostics and therapeutics. Multicomponent gold-iron oxide nanoparticles have shown high potential as contrast agents in numerous imaging techniques due to the complementary features of iron oxide and gold nanomaterials. In this paper we describe novel gold-iron oxide Janus magnetic-plasmonic nanoparticles as versatile nanoprobes for multimodal imaging. The nanoparticles are characterized as contrast agents for different imaging techniques, including X-ray computed tomography (CT), T 2 -weighted nuclear magnetic resonance imaging (MRI), photoacoustic imaging (PA), dark-field and bright-field optical microscopy, transmission electron microscopy (TEM), and surface enhanced Raman spectroscopy (SERS). We discuss the effect of particle size and morphology on their performance as contrast agents and show the advantage of a Janus configuration. Additionally, the uptake of nanoparticles by cells can be simultaneously visualized in dark- and bright-field optical microscopy, SERS mapping, and electron microscopy. These complementary techniques allow a complete view of cell uptake in an artifact-free manner, with multiplexing capabilities, and with extra information regarding the nanoparticles' fate inside the cells. Altogether, the results obtained with these non-invasive techniques show the high versatility of these nanoparticles, the advantages of a Janus configuration, and their high potential in multipurpose biomedical applications.

Circulating DNA (ctDNA) and specifically the detection cancer-associated mutations in liquid biopsies promises to revolutionize cancer detection. The main difficulty however is that the length of typical ctDNA fragments (∼150 bases) can form secondary structures potentially obscuring the mutated fragment from detection. We show that an assay based on gold nanoparticles (65 nm) stabilized with DNA (Au@DNA) can discriminate single nucleotide polymorphism in clinically relevant ssDNA sequences (70-140 bases). The preincubation step was crucial to this process, allowing sequential bridging of Au@DNA, so that single base mutation can be discriminated, down to 100 pM concentration.

Understanding protein amyloidogenesis is an important topic in protein science, fueled by the role of amyloid aggregates, especially oligomers, in the etiology of a number of devastating human degenerative diseases. However, the mechanisms that determine the formation of amyloid oligomers remain elusive due to the high complexity of the amyloidogenesis process. For instance, gold nanoparticles promote or inhibit amyloid fibrillation. We have functionalized gold nanorods with a metal-chelating group to selectively immobilize soluble RepA-WH1, a model synthetic bacterial prionoid, using a hexa-histidine tag (H6). H6-RepA-WH1 undergoes stable amyloid oligomerization in the presence of catalytic concentrations of anisotropic nanoparticles. Then, in a physically separated event, such oligomers promote the growth of amyloid fibers of untagged RepA-WH1. SERS spectral changes of H6-RepA-WH1 on spherical citrate-AuNP substrates provide evidence for structural modifications in the protein, which are compatible with a gradual increase in β-sheet structure, as expected in amyloid oligomerization., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Gold nanoparticles are prime candidates for cancer thermotherapy. However, while the ultimate target for nanoparticle-mediated photothermal therapy is the cancer cell, heating performance has not previously been evaluated in the tumoral environment. A systematic investigation of gold nanostar heat-generating efficiency in situ is presented: not only in cancer cells in vitro but also after intratumoral injection in vivo. It is demonstrated that (i) in aqueous dispersion, heat generation is governed by particle size and exciting laser wavelength; (ii) in cancer cells in vitro, heat generation is still very efficient, but irrespective of both particle size and laser wavelength; and (iii) heat generation by nanostars injected into tumors in vivo evolves with time, as the nanostars are trafficked from the extracellular matrix into endosomes. The plasmonic heating response thus serves as a signature of nanoparticle internalization in cells, bringing the ultimate goal of nanoparticle-mediated photothermal therapy a step closer., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Detection technologies employing optically encoded particles have gained much interest toward clinical diagnostics and drug discovery, but the portfolio of available systems is still limited. The fabrication and characterization of highly stable surface-enhanced resonance Raman scattering (SERRS)-encoded colloids for the identification and imaging of proteins expressed in cells are reported. These plasmonic nanostructures are made of gold octahedra coated with poly(N-isopropylacrylamide) microgels and can be readily encoded with Raman active dyes while retaining high colloidal stability in biofluids. A layer-by-layer polyelectrolyte coating is used to seal the outer surface of the encoded particles and to provide a reactive surface for covalent conjugation with antibodies. The targeted multiplexing capabilities of the SERRS tags are demonstrated by the simultaneous detection and imaging of three tumor-associated surface biomarkers: epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM), and homing cell adhesion molecule (CD44) by SERRS spectroscopy. The plasmonic microgels are able to discriminate tumor A431 (EGFR+/EpCAM+/CD44+) and nontumor 3T3 2.2 (EGFR-/EpCAM-/CD44+) cells while cocultured in vitro., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We present a general route for the transfer of Au and Ag nanoparticles of different shapes and sizes, from water into various organic solvents. The experimental conditions for each type of nanoparticles were optimized by using a combination of thiolated poly(ethylene glycol) and a hydrophobic capping agent, such as dodecanethiol. The functionalized nanoparticles were readily transferred into organic dispersions with long-term stability (months). Such organic dispersions efficiently spread out on water, leading to self-assembly at the air/liquid interface into extended nanoparticle arrays which could in turn be transferred onto solid substrates. The dense close packing in the obtained nanoparticle monolayers results in extensive plasmon coupling, rendering them efficient substrates for surface-enhanced Raman scattering spectroscopy.

Inspired by the concept of living polymerization reaction, we are able to produce silver-gold-silver nanowires with a precise control over their total length and plasmonic properties by establishing a constant silver deposition rate on the tips of penta-twinned gold nanorods used as seed cores. Consequently, the length of the wires increases linearly in time. Starting with ∼210 nm × 32 nm gold cores, we produce nanowire lengths up to several microns in a highly controlled manner, with a small self-limited increase in thickness of ∼4 nm, corresponding to aspect ratios above 100, whereas the low polydispersity of the product allows us to detect up to nine distinguishable plasmonic resonances in a single colloidal solution. We analyze the spatial distribution and the nature of the plasmons by electron energy loss spectroscopy and obtain excellent agreement between measurements and electromagnetic simulations, clearly demonstrating that the presence of the gold core plays a marginal role, except for relatively short wires or high-energy modes.

The library of plasmonic nanosystems keeps expanding with novel structures with the potential to provide new solutions to old problems in science and technology. We report the synthesis of a novel plasmonic system based on the growth of gold nanowires radially branching from the surface of silica particles. The nanowires length could be controlled by tuning the molar ratio between metal salt and surface-grafted seeds. Electron microscopy characterization revealed that the obtained one-dimensional nanoparticles are polycrystalline but uniformly distributed on the spherical template. The length of the nanowires in turn determines the optical response of the metallodielectric particles, so that longer wires display red-shifted longitudinal plasmon bands. Accurate theoretical modeling of these complex objects revealed that the densely organized nanowires display intrinsically coupled plasmon modes that can be selectively decoupled upon detachment of the nanowires from the surface of the colloidal silica template., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We report a robust and recyclable 'dip-catalyst' based on a gold nanoparticle (Au NP)-loaded filter paper composite, prepared by a simple dip-coating process using concentrated Au NP suspensions in toluene. While acting as catalysts, the composites display excellent surface enhanced Raman scattering (SERS) efficiency, allowing the real-time monitoring of chemical reactions.

Poly(ethylene glycol) (PEG) has become the gold standard for stabilization of plasmonic nanoparticles (NPs) in biofluids, because it prevents aggregation while minimizing unspecific interactions with proteins. Application of Au NPs in biological environments requires the use of ligands that can target selected receptors, even in the presence of protein-rich media. We demonstrate here the stabilizing effect of low-molecular-weight glycans on both spherical and rod-like plasmonic NPs under physiological conditions, as bench-marked against the well-established PEG ligands. Glycan-coated NPs are resistant to adsorption of proteins from serum-containing media and avoid phagocytosis by macrophage-like cells, but retain selectivity toward carbohydrate-binding proteins in protein-rich biological media. These results open the way toward the design of efficient therapeutic/diagnostic glycan-decorated plasmonic nanotools for specific biological applications.

Development of novel surface-enhanced Raman scattering (SERS) substrates and how they interface target analytes plays a pivotal role in determining the spectrum profile and SERS enhancement magnitude, as well as their applications. We present here the seed-mediated growth of reduced graphene oxide-gold nanostar (rGO-NS) nanocomposites and employ them as active SERS materials for anticancer drug (doxorubicin, DOX) loading and release. By this synthetic approach, both the morphology of rGO-NS nanohybrids and the corresponding optical properties can be precisely controlled, with no need of surfactant or polymer stabilizers. The developed rGO-NS nanohybrids show tunable optical properties by simply changing growth reaction parameters, improved stability as compared to bare Au nanostars, and sensitive SERS response toward aromatic organic molecules. Furthermore, SERS applications of rGO-NS to probe DOX loading and pH-dependent release are successfully demonstrated, showing promising potential for drug delivery and chemotherapy.

The identification of intracellular distributions of noble metal nanoparticles is of great utility for many biomedical applications. We present an effective method to distinguish intracellular from extracellular nanoparticles by selectively quenching the SERS signals from dye molecules adsorbed onto star-shaped gold nanoparticles that have not been internalized by cells.

New developments in the field of nanomaterials drive the need for quantitative characterization techniques that yield information down to the atomic scale. In this Review, we focus on the three-dimensional investigations of metal nanoparticles and their assemblies by electron tomography. This technique has become a versatile tool to understand the connection between the properties and structure or composition of nanomaterials. The different steps of an electron tomography experiment are discussed and we show how quantitative three-dimensional information can be obtained even at the atomic scale., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Gold nanorods (AuNRs) have become some of the most used nanostructures for biosensing and imaging applications due to their plasmon-related optical response, which is highly sensitive toward minute changes in the AuNR aspect ratio. In this context, H2O2 has been used to trigger the chemical etching of AuNRs, thereby inducing a decrease of their aspect ratio. However, special conditions and relatively high concentrations of H2O2 are usually required, preventing the applicability of the system for biodetection purposes. To overcome this limitation we have introduced a biocatalytic species, the enzyme horseradish peroxidase (HRP) that is able to induce a gradual oxidation of AuNRs in the presence of trace concentrations of H2O2. Interestingly, the presence of halide ions has also been found to be essential for this process. As a consequence, other enzymatic reactions, such as those catalyzed by glucose oxidase, can be easily coupled to HRP activity, allowing the detection of different amounts of glucose. On the basis of these findings, we developed a highly sensitive and simple colorimetric assay that can be read out by the naked eye and allows the detection of physiological glucose concentrations in human serum.

We present a simple procedure for the synthesis of quasi-spherical Au nanoparticles in a wide size range mediated by macrocyclic host molecules, ammonium pillar[5]arene (AP[5]A). The strategy is based on a seeded growth process in which the water-soluble pillar[5]arene undergoes complexation of the Au salt through the ammonium groups, thereby avoiding Au nucleation, while acting as a stabilizer. The presence of the pillar[5]arene onto the Au nanoparticle particle surface is demonstrated by surface-enhanced Raman scattering (SERS) spectroscopy, and the most probable conformation of the molecule when adsorbed on the Au nanoparticles surface is suggested on the basis of theoretical calculations. In addition, we analyze the host-guest interactions of the AP[5]A with 2-naphthoic acid (2NA) by using (1)H NMR spectroscopy and the results are compared with theoretical calculations. Finally, the promising synergetic effects of combining supramolecular chemistry and metal nanoparticles are demonstrated through SERS detection in water of 2NA and a polycyclic aromatic hydrocarbon, pyrene (PYR)., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Gold nanoparticles display a unique combination of chemical inertness, surface chemistry and size- and shape-dependent electronic and optical properties, which render them ideal for clinical applications., Areas Covered: The present article describes recent advancements on the application of gold nanoparticles in vaccine development and gene therapy, with augmented efficiencies in cell uptake, specific binding to bioreceptors in cells, protection of conjugated biomolecules and so forth. Additionally, we discuss how the electronic structure of the nanoparticles can be exploited for enhanced radiotherapy and X-ray tomography, while their optical properties can be used for photothermal cancer therapy or light-triggered drug delivery systems for enhanced chemotherapy., Expert Opinion: We analyze certain critical aspects and possible challenges that should be solved in order to use gold nanoparticle conjugates in vaccine research, as well as on the potential combination of properties to improve gene therapy and cancer treatment.

"The possibility of using colloidal silver and gold as condensors for electron storage in artificial photosynthesis has prompted the recent renewed interest in these areas." This statement by Fendler and co-workers in 1983 is even more relevant in today's science and technology. In this tutorial review we summarize research regarding the use of light in the synthesis of metallic nanoparticles. We describe how light of different energies induces a variety of chemical events that culminate in the nucleation and growth of metal nanocrystals. Light can thus be used as a handle to direct metal nanocrystal growth and improve tunability and reproducibility.

Quantum dot based thermometry, in combination with double beam confocal microscopy, was used to investigate the absorption/heating efficiency of gold nanoparticles with different morphologies (nanorods, nanocages, nanoshells, and nanostars), all of them with an intense localized surface plasmon resonance within the first biological window, at around 808 nm. The heating efficiency was found to be strongly dependent on the geometry of the nanostructure, with the largest values found for gold nanorods and long-edge gold nanostars, both of them with heating efficiencies close to 100%. Gold nanorods and nanocages were found to have the largest absorption cross section per unit mass among all the studied geometries, emerging as optimum photothermal agents with minimum metal loading for biosystems.

The concept of protecting groups, widely used in organic chemistry, has been applied for the synthesis of Au-silica Janus stars, in which gold branches protrude from one half of Au-silica Janus spheres. This configuration opens up new possibilities to apply the plasmonic properties of gold nanostars, as well as a variety of chemical functionalizations on the silica component.

We describe a simple and efficient methodology for the aqueous synthesis of stable, uniform, and size tunable Au@Ag core-shell nanoparticles (NPs) that are stabilized by citrate ions. The synthetic route is based on the stepwise Ag reduction on preformed Au NPs. The final size of the core-shell NPs and therefore their optical properties can be modulated at least from 30 to 110 nm by either tuning the Ag shell thickness or changing the size of the Au core. The optical properties of the Au@Ag core-shell NPs resemble those of pure Ag NPs of similar sizes, which was confirmed by means of Mie extinction calculations. We additionally evaluated the surface-enhanced raman scattering (SERS) enhancing properties of Au@Ag core-shell NP colloids with three different laser lines (532, 633, and 785 nm). Importantly, such core-shell NPs also exhibit a higher SERS efficiency than Ag NPs of similar size under near-infrared excitation. The results obtained here serve as a basis to select Au@Ag core-shell NPs of specific size and composition with maximum SERS efficiency at their respective excitation wavelengths for SERS-based analytical and bioimaging applications.

A single nanoplatform integrating laser-induced heat generation by gold nanoparticles and temperature sensing up to 2000 K via (Gd,Yb,Er)2 O3 nanorods is demonstrated, which presents considerable potential for nanoscale photonics and biomedicine. Blackbody emission is ascertained from the temperature increment with AuNP concentration, emission color coordinates as a function of the laser pump power, and Planck's law of blackbody radiation., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The dependence of the spectral width of the longitudinal localized surface plasmon resonance (LSPR) of individual gold nanorods protected by a silica shell is investigated as a function of their size. Experiments were performed using the spatial modulation spectroscopy technique that permits determination of both the spectral characteristics of the LSPR of an individual nanoparticle and its morphology. The measured LSPR is shown to broaden with reduction of both the nanorod length and its diameter, which is in contrast with the predictions of existing classical and quantum theoretical models. This behavior can be reproduced assuming the LSPR width linearly depends on the inverse of an effective length proportional to the square root of the particle surface with the same slope as that recently determined for silica-coated silver nanospheres.

Nanoplasmonics is a rapidly developing field of research and technology that is based on the ability of small metal particles to interact strongly with light of wavelength significantly larger than their size. The development of nanoplasmonics has been closely associated with the application of colloid science to the controlled growth of metal nanocrystals in solution and to directing the self-assembly of such nanocrystals into organized arrays with enhanced collective properties. Engineering the morphology and the assembly of metal nanoparticles is a key step toward the fabrication of devices with great potential in detection and diagnosis as well as in a wide variety of other fields. In this Feature Article, we provide an overview of the recent work in our laboratory, which in our view somehow reflects the evolution of the field itself and provides guidelines for future research.

In this viewpoint we discuss the early contribution from Brust et al., which is not only the most cited paper ever published in Chem. Commun., but also a landmark in gold nanoparticle research and in nanotechnology. We provide here an overview of its major contributions and how the field has evolved since its publication in 1994.

The inherent properties of silica, such as optical transparency, high biocompatibility, chemical and colloidal stability, controllable porosity, and easy surface modification, provide silica materials with a tremendous potential in biomedicine. Therefore, the coating of Au nanoparticles with silica largely contributes to enhance the important applications of metal nanoparticles in biomedicine. We describe in this chapter a number of reliable strategies that have been reported for silica coating of different types of Au nanoparticles. All descriptions are based on tested protocols and are expected to provide a reference for scientists with an interest in this field.

Surfactant-coated microbubbles are utilized in a wide variety of applications, from wastewater purification to contrast agents in medical ultrasound imaging. In many of these applications, the stability of the microbubbles is crucial to their effectiveness. Controlling this, however, represents a considerable challenge. In this study, the potential for stabilizing microbubbles using solid nanoparticles adsorbed onto their surfaces was explored. A new theoretical model has been developed to describe the influence of interfacially adsorbed solid particles upon the dissolution of a gas bubble in a liquid. The aim of this work was to test experimentally the prediction of the model that the presence of the nanoparticles would inhibit gas diffusion and coalescence/disproportionation, thus increasing the life span of the bubbles. Near-monodisperse microbubbles (~100 μm diameter) were prepared using a microfluidic device and coated with a surfactant, with and without the addition of a suspension of spherical gold nanoparticles (~15 nm diameter). The experimental results confirmed the theoretical predictions that as the surface concentration of gold nanoparticles increased the bubbles underwent negligible changes in their size and size distribution over a period of 30 days at the ambient temperature and pressure. Under the same conditions, bubbles coated with the same surfactant but no nanoparticles survived only a matter of hours.

The effects of the dielectric environment on the optical extinction spectra of gold nanorods were quantitatively studied using individual bare and silica-coated nanorods. The dispersion and amplitude of their extinction cross-section, dominated by absorption for the investigated sizes, were measured using spatial modulation spectroscopy (SMS). The experimental results were compared to calculations from a numerical model that included environmental features present in the measurements and the morphology and size of the corresponding nanorods measured by transmission electron microscopy. The combination of these experimental and theoretical tools permits a detailed interpretation of the optical properties of the individual nanorods. The measured optical extinction spectra and the extinction cross-section amplitudes were well reproduced by the numerical model for silica-coated gold nanorods, for which the silica shell provides a controlled environment. In contrast, additional environmental factors had to be assumed in the model for bare nanorods, stressing the importance of controlling and characterizing the experimental conditions when measuring the optical response of bare surface-deposited single metal nanoparticles.

In this Article, we report on the assembly of hybrid Au@PNIPAM core-shell particles at the air/water interface, their transfer onto solid substrates, and the controlled combustion of the organic material to produce arrays of gold nanoparticles. A detailed investigation on the assembly behavior of such soft hybrid colloids at the air/water interface was performed by correlating the surface pressure-area isotherms with SEM and AFM images from samples transferred at different surface pressures. The hybrid particles display a complex behavior at the interface, and we could distinguish three distinct phases with varying interparticle spacings at different compression. The transfer process presented enables the decoration of topologically structured substrates with gold nanoparticle arrays, and the order of the initial monolayers is retained in the arrays of inorganic gold nanoparticles. The change in monolayer morphology upon compression can therefore be used to tailor the interparticle distance between approximately 650 and 300 nm without exchanging the colloids. More sophisticated gold nanostructures can be patterned into symmetric arrays using a similar protocol, which we demonstrate for nanostars and nanorods.

The optical response of nanoplasmonic colloids in disperse phase is strictly related to their shape. However, upon self-assembly, new optical features, for example, bonding or antibonding modes, emerge as a result of the mutual orientations of nanoparticles. The geometry of the final assemblies often determines which mode is dominating in the overall optical response. These new plasmon modes, however, are mostly observed in silico, as self-assembly in the liquid phase leads to cluster formation with a broad range of particle units. Here we show that low-symmetry clustering of gold nanorods (AuNRs) in solution can also reveal antibonding modes. We found that UV-light irradiation of colloidal dispersions of AuNRs in N-methyl-2-pyrrolidone (NMP), stabilized by poly(vinylpyrrolidone) (PVP) results in the creation of AuNRs clusters with ladderlike morphology, where antibonding modes can be identified. We propose that UV irradiation induces formation of radicals in solvent molecules, which then promote cross-linking of PVP chains on the surface of adjacent particles. This picture opens up a number of relevant questions in nanoscience and is expected to find application in light induced self-assembly of particles with various compositions and morphologies.

Insulin-capped gold nanoparticles (Au@insulin NPs) are highly sensitive towards pH and heavy metals, due to the protein coating. Au@insulin NPs aggregate and disaggregate reversibly with pH and in the presence of various heavy metal ions, which can be monitored through reversible changes in their optical properties. The sensitivity of the NPs towards different metal ions is dissimilar and depends on the coordinative properties of each specific metal ion, its valence number, concentration, and reaction time (kinetics), representing a simple tool for studying fundamental metal-protein interactions. Moreover, Au@insulin NPs are biocompatible and highly stable at high ionic strengths, due to their robust protein coating., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Particle shape plays an important role in controlling the optical, magnetic, and mechanical properties of nanoparticle suspensions as well as nanocomposites. However, characterizing the size, shape, and the associated polydispersity of nanoparticles is not straightforward. Electron microscopy provides an accurate measurement of the geometric properties, but sample preparation can be laborious, and to obtain statistically relevant data many particles need to be analyzed separately. Moreover, when the particles are suspended in a fluid, it is important to measure their hydrodynamic properties, as they determine aspects such as diffusion and the rheological behavior of suspensions. Methods that evaluate the dynamics of nanoparticles such as light scattering and rheo-optical methods accurately provide these hydrodynamic properties, but do necessitate a sufficient optical response. In the present work, three different methods for characterizing nonspherical gold nanoparticles are critically compared, especially taking into account the complex optical response of these particles. The different methods are evaluated in terms of their versatility to asses size, shape, and polydispersity. Among these, the rheo-optical technique is shown to be the most reliable method to obtain hydrodynamic aspect ratio and polydispersity for nonspherical gold nanoparticles for two reasons. First, the use of the evolution of the orientation angle makes effects of polydispersity less important. Second, the use of an external flow field gives a mathematically more robust relation between particle motion and aspect ratio, especially for particles with relatively small aspect ratios.

Highly organized supercrystals of Au nanorods with plasmonic antennae enhancement of electrical field have made possible fast direct detection of prions in complex biological media such as serum and blood. The nearly perfect three-dimensional organization of nanorods render these systems excellent surface enhanced Raman scattering spectroscopy substrates with uniform electric field enhancement, leading to reproducibly high enhancement factor in the desirable spectral range.

Nanoparticles (NPs) can offer many advantages over traditional drug design and delivery, as well as toward medical diagnostics. As with any medical device or pharmaceutical drug intended to be used for in vivo biomedical applications, NPs must be sterile. However, very little is known regarding the effect of sterilization methods on the intrinsic properties and stability of NPs. Herein a detailed analysis of physicochemical properties of two types of AuNPs upon sterilization by means of five different techniques is reported. In addition, cell viability and production of reactive oxygen species are studied. The results indicate that sterilization by ethylene oxide seems to be the most appropriate technique for both types of NPs. It is concluded that it is crucial to test several methods in order to establish the specific type of sterilization to be performed for each particular NP.

Novel colloidal composites have been designed to incorporate multiple functionalities that allow optical detection, magnetic manipulation, molecular trapping, and thermal response. Such particles are made of gold nanoparticle cores covered by a thin layer of metallic nickel and a poly(N-isopropylacrylamide) (pNIPAM) shell. While the gold cores provide efficient optical response through localized surface plasmon resonances, nickel allows external magnetic manipulation and the pNIPAM shell can be swollen or collapsed as a function of temperature, thus allowing capture and release of various types of molecules.

We report the formation of porous gold nanoparticles with unusual, angled shapes (such as nanocheckmarks) through spontaneous transformation of tellurium sacrificial templates by gradual galvanic replacement. High-resolution electron microscopy studies of intermediate stages reveal interesting information regarding the replacement mechanism, which involves initial "gold island growth" at the edges, and gradual branching to engulf the entire particle templates, resulting in a highly porous structure. Additionally, the high porosity of these novel nanostructures with unusual shapes is demonstrated to provide very high enhancement of the Raman scattering signal from adsorbed molecules.