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 DNAgold 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 Levy-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.

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.

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 acidcoated 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.

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.

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.

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.

Silica shell growth on lanthanide-doped upconversion nanoparticles.

We demonstrate the fabrication of a new DNA sensor that is based on the optical interactions occurring between oligonucleotide-coated NaYF4:Yb3+;Er3+ upconversion nanoparticles and the two-dimensional dichalcogenide materials, MoS2 and WS2. Monodisperse upconversion nanoparticles were functionalized with single-stranded DNA endowing the nanoparticles with the ability to interact with the surface of the two-dimensional materials via van der Waals interactions leading to subsequent quenching of the upconversion fluorescence. By contrast, in the presence of a complementary oligonucleotide target and the formation of double-stranded DNA, the upconversion nanoparticles could not interact with MoS2 and WS2, thus retaining their inherent fluorescence properties. Utilizing this sensor we were able to detect target oligonucleotides with high sensitivity and specificity whilst reaching a concentration detection limit as low as 5 mol·L−1, within minutes.