Reversible Modulation of Plasmonic Coupling of Gold Nanoparticles Confined within Swellable Polymer Colloidal Spheres.

Dynamic optical modulation in response to stimuli provides exciting opportunities for designing novel sensing, actuating, and authentication devices. Here, we demonstrate that the reversible swelling and deswelling of crosslinked polymer colloidal spheres in response to pH and temperature changes can be utilized to drive the assembly and disassembly of the embedded gold nanoparticles (AuNPs), inducing their plasmonic coupling and decoupling and, correspondingly, color changes. The multi-responsive colloids are created by depositing a monolayer of AuNPs on the surface of resorcinol-formaldehyde (RF) nanospheres, then overcoating them with an additional RF layer, followed by a seeded growth process to enlarge the AuNPs and reduce their interparticle separation to induce significant plasmonic coupling. This configuration facilitates dynamic modulation of plasmonic coupling through the reversible swelling/deswelling of the polymer spheres in response to pH and temperature changes. The rapid and repeatable transitions between coupled and decoupled plasmonic states of AuNPs enable reversible color switching when the polymer spheres are in colloidal form or embedded in hydrogel substrates. Furthermore, leveraging the photothermal effect and stimuli-responsive plasmonic coupling of the embedded AuNPs enables the construction of hybrid hydrogel films featuring switchable anticounterfeiting patterns, showcasing the versatility and potential of this multi-stimuli-responsive plasmonic system.

An Investigation into the Resistance of Spherical Nucleic Acids against DNA Enzymatic Degradation.

Nanoparticles coated with oligonucleotides, also termed spherical nucleic acids (SNAs), are at the forefront of scientific research and have been applied in vitro and in vivo for sensing, gene regulation, and drug delivery. They demonstrate unique properties stemming from the three-dimensional shell of oligonucleotides and present high cellular uptake. However, their resistance to enzymatic degradation is highly dependent on their physicochemical characteristics. In particular, the oligonucleotide loading of SNAs has been determined to be a critical parameter in SNA design. In order to ensure the successful function of SNAs, the degree of oligonucleotide loading has to be quantitatively determined to confirm that a dense oligonucleotide shell has been achieved. However, this can be time-consuming and may lead to multiple syntheses being required to achieve the necessary degree of surface functionalization. In this work we show how this limitation can be overcome by introducing an oligonucleotide modification. By replacing the phosphodiester bond on the oligonucleotide backbone with a phosphorothioate bond, SNAs even with a low DNA loading showed remarkable stability in the presence of nucleases. Furthermore, these chemically modified SNAs exhibited high selectivity and specificity toward the detection of mRNA in cellulo.

Chemically modified nucleic acids and DNA intercalators as tools for nanoparticle assembly.

The self-assembly of inorganic nanoparticles to larger structures is of great research interest as it allows the fabrication of novel materials with collective properties correlated to the nanoparticles' individual characteristics. Recently developed methods for controlling nanoparticle organisation have enabled the fabrication of a range of new materials. Amongst these, the assembly of nanoparticles using DNA has attracted significant attention due to the highly selective recognition between complementary DNA strands, DNA nanostructure versatility, and ease of DNA chemical modification. In this review we discuss the application of various chemical DNA modifications and molecular intercalators as tools for the manipulation of DNA-nanoparticle structures. In detail, we discuss how DNA modifications and small molecule intercalators have been employed in the chemical and photochemical DNA ligation in nanostructures; DNA rotaxanes and catenanes associated with reconfigurable nanoparticle assemblies; and DNA backbone modifications including locked nucleic acids, peptide nucleic acids and borane nucleic acids, which affect the stability of nanostructures in complex environments. We conclude by highlighting the importance of maximising the synergy between the communities of DNA chemistry and nanoparticle self-assembly with the aim to enrich the library of tools available for the manipulation of nanostructures.

The Role of Ligands in the Chemical Synthesis and Applications of Inorganic Nanoparticles.

The design of nanoparticles is critical for their efficient use in many applications ranging from biomedicine to sensing and energy. While shape and size are responsible for the properties of the inorganic nanoparticle core, the choice of ligands is of utmost importance for the colloidal stability and function of the nanoparticles. Moreover, the selection of ligands employed in nanoparticle synthesis can determine their final size and shape. Ligands added after nanoparticle synthesis infer both new properties as well as provide enhanced colloidal stability. In this article, we provide a comprehensive review on the role of the ligands with respect to the nanoparticle morphology, stability, and function. We analyze the interaction of nanoparticle surface and ligands with different chemical groups, the types of bonding, the final dispersibility of ligand-coated nanoparticles in complex media, their reactivity, and their performance in biomedicine, photodetectors, photovoltaic devices, light-emitting devices, sensors, memory devices, thermoelectric applications, and catalysis.

Sensing of Vimentin mRNA in 2D and 3D Models of Wounded Skin Using DNA-Coated Gold Nanoparticles.

Wound healing is a highly complex biological process, which is accompanied by changes in cell phenotype, variations in protein expression, and the production of active biomolecules. Currently, the detection of proteins in cells is done by immunostaining where the proteins in fixed cells are detected by labeled antibodies. However, immunostaining cannot provide information about dynamic processes in living cells, within the whole tissue. Here, an easy method is presented to detect the transition of epithelial to mesenchymal cells during wound healing. The method employs DNA-coated gold nanoparticle fluorescent nanoprobes to sense the production of Vimentin mRNA expressed in mesenchymal cells. Fluorescence microscopy is used to achieve temporal detection of Vimentin mRNA in wounds. 3D light-sheet microscopy is utilized to observe the dynamic expression of Vimentin mRNA spatially around the wounded site in skin tissue. The use of DNA-gold nanoprobes to detect mRNA expression during wound healing opens up new possibilities for the study of real-time mechanisms in complex biological processes.

Spectroscopic and Hydrodynamic Characterisation of DNA-Linked Gold Nanoparticle Dimers in Solution using Two-Photon Photoluminescence.

Two-photon photoluminescence (TPPL) emission spectra of DNA-gold nanoparticle (AuNP) monoconjugates and the corresponding DNA-linked AuNP dimers are obtained by photon time-of-flight spectroscopy. This technique is combined with two-photon photoluminescence fluctuation correlation spectroscopy (TPPL-FCS) to simultaneously monitor the optical and hydrodynamic behaviour of these nano-assemblies in solution, with single-particle sensitivity and microsecond temporal resolution. In this study, the AuNPs have an average core diameter of 12 nm, which renders their dark-field plasmonic light scattering too weak for single-particle imaging. Moreover, as a result of the lack of plasmonic coupling in the dimers, the optical extinction, scattering and photoluminescence spectra of the DNA-AuNP complexes are not sufficiently different to distinguish between monomers and dimers. The use of TPPL-FCS successfully addresses these bottlenecks and enables the distinction between AuNP monomers and AuNP dimers in solution by measurement of their hydrodynamic rotational and translational diffusion.

Potentiating angiogenesis arrest in vivo via laser irradiation of peptide functionalised gold nanoparticles.

BACKGROUND: Anti-angiogenic therapy has great potential for cancer therapy with several FDA approved formulations but there are considerable side effects upon the normal blood vessels that decrease the potential application of such therapeutics. Chicken chorioallantoic membrane (CAM) has been used as a model to study angiogenesis in vivo. Using a CAM model, it had been previously shown that spherical gold nanoparticles functionalised with an anti-angiogenic peptide can humper neo-angiogenesis. RESULTS: Our results show that gold nanoparticles conjugated with an anti-angiogenic peptide can be combined with visible laser irradiation to enhance angiogenesis arrest in vivo. We show that a green laser coupled to gold nanoparticles can achieve high localized temperatures able to precisely cauterize blood vessels. This combined therapy acts via VEGFR pathway inhibition, leading to a fourfold reduction in FLT-1 expression. CONCLUSIONS: The proposed phototherapy extends the use of visible lasers in clinics, combining it with chemotherapy to potentiate cancer treatment. This approach allows the reduction of dose of anti-angiogenic peptide, thus reducing possible side effects, while destroying blood vessels supply critical for tumour progression.

Manganese doped-iron oxide nanoparticle clusters and their potential as agents for magnetic resonance imaging and hyperthermia.

A simple, one pot method to synthesize water-dispersible Mn doped iron oxide colloidal clusters constructed of nanoparticles arranged into secondary flower-like structures was developed. This method allows the successful incorporation and homogeneous distribution of Mn within the nanoparticle iron oxide clusters. The formed clusters retain the desired morphological and structural features observed for pure iron oxide clusters, but possess intrinsic magnetic properties that arise from Mn doping. They show distinct performance as imaging contrast agents and excellent characteristics as heating mediators in magnetic fluid hyperthermia. It is expected that the outcomes of this study will open up new avenues for the exploitation of doped magnetic nanoparticle assemblies in biomedicine.

The adsorbed state of a thiol on palladium nanoparticles.

In the present work, a combination of imaging, spectroscopic and computational methods shows that 1-dodecanethiol undergoes S-deprotonation to form 1-dodecanethiolate on the surface of palladium nanoparticles, which then self-assembles into a structure that shows a high degree of order. The alkyl chain is largely in the all-trans conformation, which occurs despite the small size of the nanoparticle, (mean diameter = 3.9 nm). Inelastic neutron scattering spectroscopy is readily able to characterise organic surface layers on nanoparticles; the nature of the material is irrelevant: whether the nanoparticle core is an oxide, a metal or a semiconductor makes no difference. Comparison to DFT calculations allows insights into the nature and conformation of the adsorbed layer.

Reversible Ligation of Programmed DNA-Gold Nanoparticle Assemblies.

We demonstrate a new method to reversibly cross-link DNA-nanoparticle dimers, trimers, and tetramers using light as an external stimulus. A DNA interstrand photo-cross-linking reaction is possible via ligation of a cyano-vinyl carbazole nucleoside with an opposite thymine when irradiated at 365 nm. This reaction results in nanoparticle assemblies that are not susceptible to DNA dehybridization conditions. The chemical bond between the two complementary DNA strands can be reversibly broken upon light irradiation at 312 nm. This is the first example of reversible ligation in DNA-nanoparticle assemblies using light and enables new developments in the field of programmed nanoparticle organization.

Interactions of skin with gold nanoparticles of different surface charge, shape, and functionality.

The interactions between skin and colloidal gold nanoparticles of different physicochemical characteristics are investigated. By systematically varying the charge, shape, and functionality of gold nanoparticles, the nanoparticle penetration through the different skin layers is assessed. The penetration is evaluated both qualitatively and quantitatively using a variety of complementary techniques. Inductively coupled plasma optical emission spectrometry (ICP-OES) is used to quantify the total number of particles which penetrate the skin structure. Transmission electron microscopy (TEM) and two photon photoluminescence microscopy (TPPL) on skin cross sections provide a direct visualization of nanoparticle migration within the different skin substructures. These studies reveal that gold nanoparticles functionalized with cell penetrating peptides (CPPs) TAT and R7 are found in the skin in larger quantities than polyethylene glycol-functionalized nanoparticles, and are able to enter deep into the skin structure. The systematic studies presented in this work may be of strong interest for developments in transdermal administration of drugs and therapy.

Colloidal branched semiconductor nanocrystals: state of the art and perspectives.

Colloidal inorganic nanocrystals are versatile nanoscale building blocks. Advances in their synthesis have yielded nanocrystals with various morphologies including spheres, polyhedra, rods, disks, sheets, wires, and a wide range of branched shapes. Recent developments in chemical methods have allowed the synthesis of colloidal nanocrystals made of sections of different inorganic materials connected together. Many research groups are investigating these nanocrystals' structural and photophysical properties experimentally and theoretically, and many have examined their prospects for commercial applications. Branched nanocrystals, in particular, are gaining attention, in part for their potential applications in solar cells or electronic devices. In this Account, we review recent developments in synthesis and controlled assembly of colloidal branched nanocrystals. Synthesis of branched nanocrystals builds on previous work with spherical nanocrystals and nanorods, but a unique factor is the need to control the branching event. Multiple arms can branch from a nucleus, or secondary branches can form from a growing arm. Branching can be governed by mechanisms including twinning, crystal splitting, polymorphism, oriented attachment, and others. One of the most relevant parameters is the choice of appropriate surfactant molecules, which can bind selectively to certain crystal facets or can even promote specific crystallographic phases during nucleation and growth. Also, seeded growth approaches recently have allowed great progress in the synthesis of nanocrystals with elaborate shapes. In this approach, nanocrystals with a specified chemical composition, size, shape, crystalline habit, and phase act as seeds on which multiple branches of a second material nucleate and grow. These approaches yield nanostructures with improved homogeneity in distribution of branch length and cross section. Ion exchange reactions allow further manipulation of branched nanocrystals by transforming crystals of one material into crystals with the same size, shape, and anion sublattice but with a new cation. Combining seeded growth with ion exchange provides a method for greatly expanding the library of branched nanocrystals. Assembly of morphologically complex nanocrystals is evolving in parallel to developments in chemical synthesis. While researchers have made many advances in the past decade in controlled assembly of nanocrystals with simple polyhedral shapes, modeling and experimental realization of ordered superstructures of branched nanocrystals are still in their infancy. In the only case of ordered superstructure reported so far, the assembly proceeds by steps in a hierarchical fashion, in analogy to several examples of assembly found in nature. Meanwhile, disordered assemblies of branched nanocrystals are also interesting and may find applications in various fields.

Hyperspectral darkfield microscopy of single hollow gold nanoparticles for biomedical applications.

Hyperspectral microscopy is a versatile method for simultaneous spatial and spectroscopic characterization of nonfluorescent samples. Here we present a hyperspectral darkfield imaging system for spectral imaging of single nanoparticles over an area of 150 × 150 µm(2) and at illumination intensities compatible with live cell imaging. The capabilities of the system are demonstrated using correlated transmission electron microscopy and single-particle optical studies of colloidal hollow gold nanoparticles. The potential of the system for characterizing the interactions between nanoparticles and cells has also been demonstrated. In this case, the spectral information proves a useful improvement to standard darkfield imaging as it enables differentiation between light scattered from nanoparticles and light scattered from other sources in the cellular environment. The combination of low illumination power and fast integration times makes the system highly suitable for nanoparticle tracking and spectroscopy in live-cell experiments.

Surfactin-Conjugated Silver Nanoparticles as an Antibacterial and Antibiofilm Agent against Pseudomonas aeruginosa.

The emergence of antimicrobial resistance is an alarming global health concern and has stimulated the development of novel functional nanomaterials to combat multi-drug-resistant (MDR) bacteria. In this work, we demonstrate for the first time the synthesis and application of surfactin-coated silver nanoparticles as an efficient antibacterial and antibiofilm agent against the drug-resistant bacteria Pseudomonas aeruginosa for safe dermal applications. Our in vivo studies showed no significant superficial dermal irritation, edema, and erythema, while microscopic analysis revealed that surfactin-coated silver nanoparticles caused no pathological alterations at the applied concentrations. These results support the potential use of surfactin-coated silver nanoparticles against drug-resistant bacterial biofilm infections and in skin wound dressing applications.

Single-cell RNA-sequence analysis of human bone marrow reveals new targets for isolation of skeletal stem cells using spherical nucleic acids.

There is a wealth of data indicating human bone marrow contains skeletal stem cells (SSC) with the capacity for osteogenic, chondrogenic and adipogenic differentiation. However, current methods to isolate SSCs are restricted by the lack of a defined marker, limiting understanding of SSC fate, immunophenotype, function and clinical application. The current study applied single-cell RNA-sequencing to profile human adult bone marrow populations from 11 donors and identified novel targets for SSC enrichment. Spherical nucleic acids were used to detect these mRNA targets in SSCs. This methodology was able to rapidly isolate potential SSCs found at a frequency of <1 in 1,000,000 in human bone marrow, with the capacity for tri-lineage differentiation in vitro and ectopic bone formation in vivo. The current studies detail the development of a platform to advance SSC enrichment from human bone marrow, offering an invaluable resource for further SSC characterisation, with significant therapeutic impact therein.

Interactions of human endothelial cells with gold nanoparticles of different morphologies.

The interactions between noncancerous, primary endothelial cells and gold nanoparticles with different morphologies but the same ligand capping are investigated. The endothelial cells are incubated with gold nanospheres, nanorods, hollow gold spheres, and core/shell silica/gold nanocrystals, which are coated with monocarboxy (1-mercaptoundec-11-yl) hexaethylene glycol (OEG). Cell viability studies show that all types of gold particles are noncytotoxic. The number of particles taken up by the cells is estimated using inductively coupled plasma (ICP), and are found to differ depending on particle morphology. The above results are discussed with respect to heating efficiency. Using experimental data reported earlier and theoretical model calculations which take into account the physical properties and distribution of particles in the cellular microenvironment, it is found that collective heating effects of several cells loaded with nanoparticles must be included to explain the observed viability of the endothelial cells.

Formation and plasmonic response of self-assembled layers of colloidal gold nanorods and branched gold nanoparticles.

The plasmonic properties of self-assembled layers of rod- and branched-shaped gold nanoparticles were investigated using optical techniques. Nanoparticles were synthesized by a surfactant-guided, seed-mediated growth method. The layers were obtained by gradual assembly of nanoparticles at the interface between a polar and a nonpolar solvent and were transferred to a glass slide. Polarization and angle-dependent extinction measurements showed that the layers made of gold nanorods were governed by an effective medium response. The response of the layers made by branched gold particles was characterized by random light scattering. Microscopic mapping of the spatial mode structure demonstrates a uniform optical response of the nanoparticle layers down to a submicrometer length scale.

Laser-induced damage and recovery of plasmonically targeted human endothelial cells.

Laser-induced techniques that employ the surface plasmon resonances of nanoparticles have recently been introduced as an effective therapeutic tool for destroying tumor cells. Here, we adopt a low-intensity laser-induced technique to manipulate the damage and repair of a vital category of noncancerous cells, human endothelial cells. Endothelial cells construct the interior of blood vessels and play a pivotal role in angiogenesis. The degree of damage and repair of the cells is shown to be influenced by laser illumination in the presence of gold nanoparticles of different morphologies, which either target the cellular membrane or are endocytosed. A pronounced influence of the plasmonic nanoparticle laser treatment on the expression of critical angiogenic genes is shown. Our results show that plasmon-mediated mild laser treatment, combined with specific targeting of cellular membranes, enables new routes for controlling cell permeability and gene regulation in endothelial cells.

A SARS-Cov-2 sensor based on upconversion nanoparticles and graphene oxide.

Since the beginning of the COVID-19 pandemic, there has been an increased need for the development of novel diagnostic solutions that can accurately and rapidly detect SARS-CoV-2 infection. In this work, we demonstrate the targeting of viral oligonucleotide markers within minutes without the requirement of a polymerase chain reaction (PCR) amplification step via the use of oligonucleotide-coated upconversion nanoparticles (UCNPs) and graphene oxide (GO).

Nanoparticle-Induced Property Changes in Nematic Liquid Crystals.

Doping liquid crystals with nanoparticles is a widely accepted method to enhance liquid crystal's intrinsic properties. In this study, a quick and reliable method to characterise such colloidal suspensions using an optical multi-parameter analyser, a cross-polarised intensity measurement-based device, is presented. Suspensions characterised in this work are either plasmonic (azo-thiol gold AzoGNPs) or ferroelectric Sn2P2S6 (SPS) nanoparticles in nematic liquid crystals. The elastic constants and rotational viscosity showed nonlinear dependence on the concentration of AzoGNPs, initially increasing at lower concentrations and then decreasing at higher concentrations, indicating some degree of particle aggregation. For the SPS suspension, the elastic constant decreased with doping, while the rotational viscosity increased, in agreement with previous findings. Through viscosity measurements, the stability of SPS suspension over ten years is also highlighted.