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).

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.

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.

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.

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.

Multiplexed mRNA Sensing and Combinatorial-Targeted Drug Delivery Using DNA-Gold Nanoparticle Dimers.

The design of nanoparticulate systems which can perform multiple synergistic functions in cells with high specificity and selectivity is of great importance in applications. Here we combine recent advances in DNA-gold nanoparticle self-assembly and sensing to develop gold nanoparticle dimers that are able to perform multiplexed synergistic functions within a cellular environment. These dimers can sense two mRNA targets and simultaneously or independently deliver one or two DNA-intercalating anticancer drugs (doxorubicin and mitoxantrone) in live cells. Our study focuses on the design of sophisticated nanoparticle assemblies with multiple and synergistic functions that have the potential to advance sensing and drug delivery in cells.