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.

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.

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.

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.

A method for the growth of uniform silica shells on different size and morphology upconversion nanoparticles.

Lanthanide-doped upconversion nanoparticles have emerged as attractive candidates for biomedical applications. This is due to their excitation and emission wavelengths, which lay the foundation for deeper penetration depth into biological tissue, higher resolution due to reduced scattering and improved imaging contrast as a result of a decrease in autofluorescence background. Usually, their encapsulation within a biocompatible silica shell is a requirement for their dispersion within complex media or for further functionalization of the upconversion nanoparticle surface. However, the creation of a silica shell around upconversion nanoparticles can be often challenging, many times resulting in partial silica coating or nanoparticle aggregation, as well as the production of a large number of silica particles as a side product. In this work we demonstrate a method to accurately predict the experimental conditions required to form a high yield of silica-coated upconversion nanoparticles, regardless of their shape and size.

DNA Gold Nanoparticle Motors Demonstrate Processive Motion with Bursts of Speed Up to 50 nm Per Second.

Synthetic motors that consume chemical energy to produce mechanical work offer potential applications in many fields that span from computing to drug delivery and diagnostics. Among the various synthetic motors studied thus far, DNA-based machines offer the greatest programmability and have shown the ability to translocate micrometer-distances in an autonomous manner. DNA motors move by employing a burnt-bridge Brownian ratchet mechanism, where the DNA "legs" hybridize and then destroy complementary nucleic acids immobilized on a surface. We have previously shown that highly multivalent DNA motors that roll offer improved performance compared to bipedal walkers. Here, we use DNA-gold nanoparticle conjugates to investigate and enhance DNA nanomotor performance. Specifically, we tune structural parameters such as DNA leg density, leg span, and nanoparticle anisotropy as well as buffer conditions to enhance motor performance. Both modeling and experiments demonstrate that increasing DNA leg density boosts the speed and processivity of motors, whereas DNA leg span increases processivity and directionality. By taking advantage of label-free imaging of nanomotors, we also uncover Lévy-type motion where motors exhibit bursts of translocation that are punctuated with transient stalling. Dimerized particles also demonstrate more ballistic trajectories confirming a rolling mechanism. Our work shows the fundamental properties that control DNA motor performance and demonstrates optimized motors that can travel multiple micrometers within minutes with speeds of up to 50 nm/s. The performance of these nanoscale motors approaches that of motor proteins that travel at speeds of 100-1000 nm/s, and hence this work can be important in developing protocellular systems as well next generation sensors and diagnostics.

Enrichment of Skeletal Stem Cells from Human Bone Marrow Using Spherical Nucleic Acids.

Human bone marrow (BM)-derived stromal cells contain a population of skeletal stem cells (SSCs), with the capacity to differentiate along the osteogenic, adipogenic, and chondrogenic lineages, enabling their application to clinical therapies. However, current methods to isolate and enrich SSCs from human tissues remain, at best, challenging in the absence of a specific SSC marker. Unfortunately, none of the current proposed markers alone can isolate a homogeneous cell population with the ability to form bone, cartilage, and adipose tissue in humans. Here, we have designed DNA-gold nanoparticles able to identify and sort SSCs displaying specific mRNA signatures. The current approach demonstrates the significant enrichment attained in the isolation of SSCs, with potential therein to enhance our understanding of bone cell biology and translational applications.

Bactericidal Effect of 5-Mercapto-2-nitrobenzoic Acid-Coated Silver Nanoclusters against Multidrug-Resistant Neisseria gonorrhoeae.

Neisseria gonorrhoeae is among the most multidrug-resistant bacteria in circulation today, and new treatments are urgently needed. In this work, we demonstrate the ability of 5-mercapto-2-nitrobenzoic acid-coated silver nanoclusters (MNBA-AgNCs) to kill strains of Neisseria gonorrhoeae. Using an in vitro bactericidal assay, MNBA-AgNCs had been found to show significantly higher anti-gonococcal bioactivity than the antibiotics ceftriaxone and azithromycin and silver nitrate. These nanoclusters were effective against both planktonic bacteria and a gonococcal infection of human cell cultures in vitro. Treatment of human cells in vitro with MNBA-AgNCs did not induce significant release of lactate dehydrogenase, suggesting minimal cytotoxicity to eukaryotic cells. Our results suggest that MNBA-AgNCs hold great potential for topical treatment of localized gonorrhoeae.

Nanoparticles-assisted delivery of antiviral-siRNA as inhalable treatment for human respiratory viruses: A candidate approach against SARS-COV-2.

The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has challenged healthcare structures across the globe. Although a few therapies are approved by FDA, the search for better treatment options is continuously on rise. Clinical management includes infection prevention and supportive care such as supplemental oxygen and mechanical ventilatory support. Given the urgent nature of the pandemic and the number of companies and researchers developing COVID-19 related therapies, FDA has created an emergency program to move potential treatments with already approved drugs to patients as quickly as possible in parallel to the development of new drugs that must first pass the clinical trials. In this manuscript, we have reviewed the available literature on the use of sequence-specific degradation of viral genome using short-interfering RNA (siRNA) suggesting it as a possible treatment against SARS-CoV-2. Delivery of siRNA can be promoted by the use of FDA approved lipids, polymers or lipid-polymer hybrids. These nanoparticulate systems can be engineered to exhibit increased targetability and formulated as inhalable aerosols.

Light-Induced Reversible DNA Ligation of Gold Nanoparticle Superlattices.

DNA-mediated self-assembly of nanoparticles has been of great interest because it enables access to nanoparticle superstructures that cannot be synthesized otherwise. However, the programmability of higher order nanoparticle structures can be easily lost under DNA denaturing conditions. Here, we demonstrate that light can be employed as an external stimulus to master the stability of nanoparticle superlattices (SLs) via the promotion of a reversible photoligation of DNA in SLs. The oligonucleotides attached to the nanoparticles are encoded to ligate using 365 nm light, effectively locking the SLs and rendering them stable under DNA denaturing conditions. The reversible process of unlocking these structures is possible by irradiation with light at 315 nm, recovering the structures to their natural state. Our work inspires an alternative research direction toward postassembly manipulation of nanoparticle superstructures using external stimuli as a tool to enrich the library of additional material forms and their application in different media and environments.

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.

DNA-Coated Gold Nanoparticles for the Detection of mRNA in Live Hydra Vulgaris Animals.

Advances in nanoparticle design have led to the development of nanoparticulate systems that can sense intracellular molecules, alter cellular processes, and release drugs to specific targets in vitro. In this work, we demonstrate that oligonucleotide-coated gold nanoparticles are suitable for the detection of mRNA in live Hydra vulgaris, a model organism, without affecting the animal's integrity. We specifically focus on the detection of Hymyc1 mRNA, which is responsible for the regulation of the balance between stem cell self-renewal and differentiation. Myc deregulation is found in more than half of human cancers, thus the ability to detect in vivo related mRNAs through innovative fluorescent systems is of outmost interest.

Biosurfactant coated silver and iron oxide nanoparticles with enhanced anti-biofilm and anti-adhesive properties.

Pseudomonas aeruginosa and Staphylococcus aureus are among the hazardous biofilm forming bacteria ubiquitous in industrial/clinical wastes. Serious efforts are required to develop effective strategies to control surface-growing antibiotic resistant pathogenic bacterial communities which they are emerging as a global health issue. Blocking hazardous biofilms would be a useful aspect of biosurfactant coated nanoparticles (NPs). In this regard, we report a facile method for the synthesis of rhamnolipid (RL) coated silver (Ag) and iron oxide (Fe3O4) NPs and propose the mechanism of their synergistic antibacterial and anti-adhesive properties against biofilms formed by P. aeruginosa and S. aureus. These NPs demonstrated excellent anti-biofilm activity not only during the biofilms formation but also on the pre-formed biofilms. Mechanistically, RL coated silver (35 nm) and Fe3O4 NPs (48 nm) generate reactive oxygen species, which contribute to the antimicrobial activity. The presence of RLs shell on the nanoparticles significantly reduces the cell adhesion by modifying the surface hydrophobicity and hence enhancing the anti-biofilm property of NPs against both mentioned strains. These findings suggest that RL coated Ag and Fe3O4 NPs may be used as potent alternate to reduce the infection severity by inhibiting the biofilm formation and, therefore, they possess potential biomedical applications for antibacterial coatings and wound dressings.

Anion exchange in inorganic perovskite nanocrystal polymer composites.

We demonstrate a facile, low-cost and room-temperature method of anion exchange in cesium lead bromide nanocrystals (CsPbBr3 NCs), embedded into a polymer matrix. The anion exchange occurs upon exposure of the solid CsPbBr3 NCs/PDMS nanocomposite to a controlled anion precursor gas atmosphere. The rate and extent of the anion exchange reaction can be controlled via the variation of either the exposure time or the relative concentration of the anion precursor gas. Post-synthesis chemical transformation of perovskite nanocrystal-polymer composites is not readily achievable using conventional methods of anion exchange, which renders the gas-assisted strategy extremely useful. We envisage that this work will enable the development of solid-state perovskite NC optoelectronic devices.

Colloidal Synthesis of CsX Nanocrystals (X = Cl, Br, I).

A facile colloidal synthesis of highly ionic cesium halide nanocrystals is reported. Colloidal nanocrystals of CsI, CsCl and CsBr with unprecedentedly small dimensions are obtained using oleylammonium halides and cesium oleate as precursors. The ease and adaptability of our method enables its universalization for the formation of other highly ionic nanocrystals.

Graphene Oxide-Upconversion Nanoparticle Based Portable Sensors for Assessing Nutritional Deficiencies in Crops.

The development of innovative technologies to rapidly detect biomarkers associated with nutritional deficiencies in crops is highly relevant to agriculture and thus could impact the future of food security. Zinc (Zn) is an important micronutrient in plants, and deficiency leads to poor health, quality, and yield of crops. We have developed portable sensors, based on graphene oxide and upconversion nanoparticles, which could be used in the early detection of Zn deficiency in crops, sensing mRNAs encoding members of the ZIP-transporter family in crops. ZIPs are membrane transport proteins, some of which are up-regulated at the early stages of Zn deficiency, and they are part of the biological mechanism by which crops respond to nutritional deficiency. The principle of these sensors is based on the intensity of the optical output resulting from the interaction of oligonucleotide-coated upconversion nanoparticles and graphene oxide in the absence or presence of a specific oligonucleotide target. The sensors can reliably detect mRNAs in RNA extracts from plants using a smartphone camera. Our work introduces the development of accurate and highly sensitive sensors for use in the field to determine crop nutrient status and ultimately facilitate economically important nutrient management decisions.

Cells on hierarchically-structured platforms hosting functionalized nanoparticles.

In this work, we report on a novel approach to develop hierarchically-structured cell culture platforms incorporating functionalized gold nanoparticles (AuNPs). In particular, the hierarchical substrates comprise primary pseudo-periodic arrays of silicon microcones combined with a secondary nanoscale pattern of homogeneously deposited AuNPs terminated with bio-functional moieties. AuNPs with various functionalities (i.e. oligopeptides, small molecules and oligomers) were successfully attached onto the microstructures. Experiments with PC12 cells on hierarchical substrates incorporating AuNPs carrying the RGD peptide showed an impressive growth and NGF-induced differentiation of the PC12 cells, compared to that on the NP-free, bare, micropatterned substrates. The exploitation of the developed methodology for the binding of AuNPs as carriers of specific bio-functional moieties onto micropatterned culture substrates for cell biology studies is envisaged.