Rapid Assembly of Magnetoplasmonic Photonic Arrays for Brilliant, Noniridescent, and Stimuli-Responsive Structural Colors.

There are usually trade-offs between maximizing the color saturation and brightness and minimizing the angle-dependent effect in structural colors. Here, a magnetic field-induced assembly for the rapid formation of scalable, uniform amorphous photonic arrays (APAs) featuring unique structural colors is demonstrated. The magnetic field plays a fundamental role in photonic film formation, making this assembly technology versatile for developing structural color patterns on arbitrary substrates. The synergistic combination of surface plasmonic resonance of the Ag core and broadband light absorption of high refractive index (RI) Fe3 O4 shell in hybrid magnetoplasmonic nanoparticles (MagPlas NPs) enables breaking the trade-offs to produce brilliant, noniridescent structural colors with high tunability and responsiveness. These features enable the fabrication of various types of highly sensitive and reliable colorimetric sensors for naked-eye detection without sophisticated instruments. Furthermore, large-scale structural color patterns are effortlessly achieved, demonstrating the high potential of the present approach for full-spectrum displays, active coatings, and rewritable papers.

Clinical Trial: Magnetoplasmonic ELISA for Urine-based Active Tuberculosis Detection and Anti-Tuberculosis Therapy Monitoring.

The coronavirus disease 2019 (COVID-19) pandemic has proved the importance of fast and widespread diagnostic testing to prevent serious epidemics timely. The first-line weapon against rapidly transmitted disease is a quick and massive screening test to isolate patients immediately, preventing dissemination. Here, we described magnetoplasmonic nanozymes (MagPlas NZs), i.e., hierarchically coassembled Fe3O4-Au superparticles, that are capable of integrating magnetic enrichment and catalytic amplification, thereby the assay can be streamlined amenable to high-throughput operation and achieve ultrahigh sensitivity. Combining this advantage with conventional enzyme-linked immunosorbent assay (ELISA), we propose a MagPlas ELISA for urine-based tuberculosis (TB) diagnosis and anti-TB therapy monitoring, which enables fast (<3 h), and highly sensitive (up to pM with naked-eyes, < 10 fM with plate reader) urinary TB antigen detection. A clinical study with a total of 297 urine samples showed robust sensitivity for pulmonary tuberculosis (85.0%) and extra-pulmonary tuberculosis (52.8%) patients with high specificity (96.7% and 96.9%). Furthermore, this methodology offers a great promise of noninvasive therapeutic response monitoring, which is impracticable in the gold-standard culture method. The MagPlas ELISA showed high sensitivity comparable to the PCR assay while retaining a simple and cheap ELISA concept, thus it could be a promising point-of-care test for TB epidemic control and possibly applied to other acute infections.

Iron-Palladium magnetic nanoparticles for decolorizing rhodamine B and scavenging reactive oxygen species.

HYPOTHESIS: Here, FePd magnetic nanoparticles (MNPs) are developed as artificial enzymes with high biocompatibility and reusability. EXPERIMENT: The nanoparticles (NPs) are synthesized in an aqueous solvent by one-pot synthesis utilizing glutathione (GSH) and cysteine (Cys) as surfactants. FINDINGS: The prepared hydrophilic FePd NPs are redispersible in water. Further, they exhibit catalytic activity for the degradation of rhodamine B (RhB), as well as for the inhibition of reactive oxygen species (ROS) production induced by H2O2, which are two- and seven-fold enhancements of their catalytic performances, respectively, compared with that of horseradish peroxidase. The computational simulation and electrochemical analysis indicate that the enhancement of the catalytic effect is due to the protection of the MNP surface by GSH and Cys. In vitro experiments reveal that FePd MNPs behave like a peroxidase and decrease the ROS in mammalian cells. The cytotoxicity assessment of FePd MNPs via exposures to different cell lines for over seven days indicates that they can maintain the cell viability of >90% for up to 20 µgmL-1 concentration. FePd MNPs with high saturation magnetization and biocompatibility can be utilized as recyclable peroxidase-mimicking nanozymes and biosensors in a variety of catalytic and biological applications.

Contralateral spreading of substances following intratympanic nanoparticle-conjugated gentamicin injection in a rat model.

This study was performed to investigate the Eustachian tube as a potential route for contralateral spreading following intratympanic nanoparticle (NP)-conjugated gentamicin injection in a rat model. Sprague-Dawley rats were divided into three groups and substances were injected in the right ear: group 1 (fluorescent magnetic nanoparticles [F-MNPs], n = 4), group 2 (F-MNP-conjugated gentamicin [F-MNP@GM], n = 2), and control group (no injections, n = 2). T2-weighted sequences corresponding to the regions of interest at 1, 2, and 3 h after intratympanic injection were evaluated, along with immunostaining fluorescence of both side cochlea. The heterogeneous signal intensity of F-MNPs and F-MNP@GM on T2-weighted images, observed in the ipsilateral tympanum, was also detected in the contralateral tympanum in 4 out of 6 rats, recapitulating fluorescent nanoparticles in the contralateral cochlear hair cells. Computational simulations demonstrate the contralateral spreading of particles by gravity force following intratympanic injection in a rat model. The diffusion rate of the contralateral spreading relies on the sizes and surface charges of particles. Collectively, the Eustachian tube could be a route for contralateral spreading following intratympanic injection. Caution should be taken when using the contralateral ear as a control study investigating inner-ear drug delivery through the transtympanic approach.

Protein arginine methyltransferase-1 stimulates dopaminergic neuronal cell death in a Parkinson's disease model.

Recent studies have revealed that protein arginine methyltransferases (PRMTs) are responsible for diverse neurodegenerative diseases. However, their pathophysiological role in dopaminergic neuronal death in Parkinson's disease (PD) has not been evaluated. In this study, we demonstrated that 1-Methyl-4-phenylpyridinium iodide (MPP+), rotenone and paraquat, which cause dopaminergic neuronal cell death, increased PRMT1 expression in dopaminergic cell line. Dopaminergic neuronal cell death was increased by PRMT1 overexpression. MPP+-induced cell death was attenuated by PRMT1 knockdown. Poly (ADP-ribose) polymerase-1 (PARP1) expression and activity, poly-ADP-ribosylation (PARylation), were elevated by MPP+. Moreover, we found that PRMT1 positively regulates nuclear translocation of apoptosis-inducing factor (AIF). Elevated PRMT1 expression was observed in the substantia nigra pars compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-injected mice. Furthermore, MPTP-induced dopaminergic neuronal death was reduced in PRMT1 haploinsufficient (prmt1+/-) mice. These data suggest that PRMT1 is implicated in PARP1/AIF-mediated dopaminergic neuronal cell death, which might be involved in the pathology of PD. Therefore, our results propose PRMT1 as a new target to develop a potential treatment of PD.

Au nanozyme-driven antioxidation for preventing frailty.

From senescence and frailty that may result from various biological, mechanical, nutritional, and metabolic processes, the human body has its own antioxidant defense enzymes to remove by-products of oxygen metabolism, and if unregulated, can cause several types of cell damage. Herein, an antioxidant, artificial nanoscale enzyme, called nanozyme (NZs), is introduced that is composed of Au nanoparticles (NPs) synthesized with a mixture of two representative phytochemicals, namely, gallic acid (GA) and isoflavone (IF), referred to as GI-Au NZs. Their unique antioxidant and anti-aging effects are monitored using Cell Counting Kit-8 and senescence-associated ß-galactosidase assays on neonatal human dermal fibroblasts (nHDFs). Furthermore, alterations in epidermal thickness and SOD activity are measured under ultraviolet light to investigate the effects of the topical application of NZs on the histological structure and antioxidant activity in hairless mice skin. Then, hepatotoxicity and nephrotoxicity in the hairless mice are monitored. It is concluded that the NZs can effectively prevent serial passage-induced senescence in nHDFs, as well as oxidative stress in mice skin, suggesting a range of strategies to further develop novel therapeutics for acute frailty.

In Vivo Study of Spiky Fe3O4@Au Nanoparticles with Different Branch Lengths: Biodistribution, Clearance, and Biocompatibility in Mice.

Magnetoplasmonic nanoparticles (Fe3O4@Au NPs) have been proven to be effective theranostic agents in genetic transmission and drug targeted delivery system as well as in photothermal treatment. Herein, two spiky magnetoplasmonic NPs with different branch lengths and numbers (short- and long-branched spiky Fe3O4@Au NPs) were specifically designed to determine theirs in vivo behaviors. The biocompatibility, biodistribution, and clearance of spiky Fe3O4@Au NPs were examined in mice. Organ distributions showed that intravenously administered spiky Fe3O4@Au NPs cumulated mainly in liver and spleen, and particle shape significantly affected their in vivo behaviors. The higher tendency in bioaccumulation of short-branched rather than long-branched spiky Fe3O4@Au NPs was observed in the spleen because long-branched spiky Fe3O4@Au NPs with a high aspect ratio were internalized more slowly than short-branched spiky Fe3O4@Au NPs. Serum biochemistry and transmission electron microscopy of ultrahistological structures indicated that spiky Fe3O4@Au NPs did not exhibit distinct toxicity in vivo and posed no potential risk of causing liver and kidney dysfunction. These findings lay the foundation for the design of future theragnostic agents.

Scalable Solvothermal Synthesis of Superparamagnetic Fe3O4 Nanoclusters for Bioseparation and Theragnostic Probes.

Magnetic nanoparticles have had a significant impact on a wide range of advanced applications in the academic and industrial fields. In particular, in nanomedicine, the nanoparticles require specific properties, including hydrophilic behavior, uniform and tunable dimensions, and good magnetic properties, which are still challenging to achieve by industrial-scale synthesis. Here, we report a gram-scale synthesis of hydrophilic magnetic nanoclusters based on a one-pot solvothermal system. Using this approach, we achieved the nanoclusters with controlled size composed of magnetite nanocrystals in close-packed superstructures that exhibited hydrophilicity, superparamagnetism, high magnetization, and colloidal stability. The proposed solvothermal method is found to be highly suitable for synthesizing industrial quantities (gram-per-batch level) of magnetic spheres with unchanged structural and magnetic properties. Furthermore, coating the magnetic spheres with an additional silica layer provided further stability and specific functionalities favorable for biological applications. Using in vitro and in vivo studies, we successfully demonstrated both positive and negative separation and the use of the magnetic nanoclusters as a theragnostic nanoprobe. This scalable synthetic procedure is expected to be highly suitable for widespread use in biomedical, energy storage, photonics, and catalysis fields, among others.

Chiral zirconium quantum dots: A new class of nanocrystals for optical detection of coronavirus.

A synthetic way of chiral zirconium quantum dots (Zr QDs) was presented for the first time using L(+)-ascorbic acid acts as a surface as well as chiral ligands. Different spectroscopic and microscopic analysis was performed for thorough characterization of Zr QDs. As-synthesized QDs exhibited fluorescence and circular dichroism properties, and the peaks were located at 412 nm and 352 nm, respectively. MTT assay was performed to test the cytotoxicity of the synthesized Zr QDs against rat brain glioma C6 cells. Synthesized QDs was further conjugated with anti-infectious bronchitis virus (IBV) antibodies of coronavirus to form an immunolink at the presence of the target analyte and anti-IBV antibody-conjugated magneto-plasmonic nanoparticles (MPNPs). The fluorescence properties of immuno-conjugated QD-MP NPs nanohybrids through separation by an external magnetic field enabled biosensing of coronavirus with a limit of detection of 79.15 EID/50 µL.

Magnetic Nanozyme-Linked Immunosorbent Assay for Ultrasensitive Influenza A Virus Detection.

Rapid and sensitive detection of influenza virus is of soaring importance to prevent further spread of infections and adequate clinical treatment. Herein, an ultrasensitive colorimetric assay called magnetic nano(e)zyme-linked immunosorbent assay (MagLISA) is suggested, in which silica-shelled magnetic nanobeads (MagNBs) and gold nanoparticles are combined to monitor influenza A virus up to femtogram per milliliter concentration. Two essential strategies for ultrasensitive sensing are designed, i.e., facile target separation by MagNBs and signal amplification by the enzymelike activity of gold nanozymes (AuNZs). The enzymelike activity was experimentally and computationally evaluated, where the catalyticity of AuNZ was tremendously stronger than that of normal biological enzymes. In the spiked test, a straightforward linearity was presented in the range of 5.0 × 10-15-5.0 × 10-6g·mL-1 in detecting the influenza virus A (New Caledonia/20/1999) (H1N1). The detection limit is up to 5.0 × 10-12 g·mL-1 only by human eyes, as well as up to 44.2 × 10-15 g·mL-1 by a microplate reader, which is the lowest record to monitor influenza virus using enzyme-linked immunosorbent assay-based technology as far as we know. Clinically isolated human serum samples were successfully observed at the detection limit of 2.6 PFU·mL-1. This novel MagLISA demonstrates, therefore, a robust sensing platform possessing the advances of fathomable sample separation, enrichment, ultrasensitive readout, and anti-interference ability may reduce the spread of influenza virus and provide immediate clinical treatment.

Enhanced Internalization of Macromolecular Drugs into Mycobacterium smegmatis with the Assistance of Silver Nanoparticles.

In this study, silver nanoparticles (AgNPs) were synthesized by the citrate reduction process and, with the assistance of n-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, were successfully loaded with the macromolecular drug vancomycin (VAM) to form AgNP-VAM bioconjugates. The synthesized AgNPs, VAM, and AgNP-VAM conjugate were characterized by UV-visible spectroscopy, zeta potential analysis, confocal microscopy, and transmission electron microscopy. The effect of loading VAM onto AgNPs was investigated by testing the internalization of the bioconjugate into Mycobacterium smegmatis. After treatment with the AgNP-VAM conjugate, the bacterial cells showed a significant decrease in UV absorption, indicating that loading of the VAM on AgNPs had vastly improved the drug's internalization compared with that of AgNPs. All the experimental assessments showed that, compared with free AgNPs and VAM, enhanced internalization had been successfully achieved with the AgNP-VAM conjugate, thus leading to significantly better delivery of the macromolecular drug into the M. smegmatis cell. The current research provides a new potential drug delivery system for the treatment of mycobacterial infections..

In vivo feasibility test using transparent carbon nanotube-coated polydimethylsiloxane sheet at brain tissue and sciatic nerve.

Carbon nanotubes, with their unique and outstanding properties, such as strong mechanical strength and high electrical conductivity, have become very popular for the repair of tissues, particularly for those requiring electrical stimuli. Polydimethylsiloxane (PDMS)-based elastomers have been used in a wide range of biomedical applications because of their optical transparency, physiological inertness, blood compatibility, non-toxicity, and gas permeability. In present study, most of artificial nerve guidance conduits (ANGCs) are not transparent. It is hard to confirm the position of two stumps of damaged nerve during nerve surgery and the conduits must be cut open again to observe regenerative nerves after surgery. Thus, a novel preparation method was utilized to produce a transparent sheet using PDMS and multiwalled carbon nanotubes (MWNTs) via printing transfer method. Characterization of the PDMS/MWNT (PM) sheets revealed their unique physicochemical properties, such as superior mechanical strength, a certain degree of electrical conductivity, and high transparency. Characterization of the in vitro and in vivo usability was evaluated. PM sheets showed high biocompatibility and adhesive ability. In vivo feasibility tests of rat brain tissue and sciatic nerve revealed the high transparency of PM sheets, suggesting that it can be used in the further development of ANGCs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1736-1745, 2017.

Synthesis of Gold Nanoparticles with Buffer-Dependent Variations of Size and Morphology in Biological Buffers.

The demand for biologically compatible and stable noble metal nanoparticles (NPs) has increased in recent years due to their inert nature and unique optical properties. In this article, we present 11 different synthetic methods for obtaining gold nanoparticles (Au NPs) through the use of common biological buffers. The results demonstrate that the sizes, shapes, and monodispersity of the NPs could be varied depending on the type of buffer used, as these buffers acted as both a reducing agent and a stabilizer in each synthesis. Theoretical simulations and electrochemical experiments were performed to understand the buffer-dependent variations of size and morphology exhibited by these Au NPs, which revealed that surface interactions and the electrostatic energy on the (111) surface of Au were the determining factors. The long-term stability of the synthesized NPs in buffer solution was also investigated. Most NPs synthesized using buffers showed a uniquely wide range of pH stability and excellent cell viability without the need for further modifications.

Ambient atmosphere-processable, printable Cu electrodes for flexible device applications: structural welding on a millisecond timescale of surface oxide-free Cu nanoparticles.

Recently, various functional devices based on printing technologies have been of paramount interest, owing to their characteristic processing advantages along with excellent device performance. In particular, printable metallic electrodes have drawn attention in a variety of optoelectronic applications; however, research into printable metallic nanoparticles has been limited mainly to the case of an environmentally stable Ag phase. Despite its earth-abundance and highly conductive nature, the Cu phase, to date, has not been exploited as an ambient atmosphere-processable, printable material due to its critical oxidation problem in air. In this study, we demonstrate a facile route for generating highly conductive, flexible Cu electrodes in air by introducing the well-optimized photonic sintering at a time frame of 10(-3) s, at which the photon energy, rather than conventional thermal energy, is instantly provided. It is elucidated here how the surface oxide-free, printed Cu particulate films undergo chemical structural/microstructural evolution depending on the instantly irradiated photon energy, and a successful demonstration is provided of large-area, flexible, printed Cu conductors on various substrates, including polyimide (PI), polyethersulfone (PES), polyethylene terephthalate (PET), and paper. The applicability of the resulting printed Cu electrodes is evaluated via implementation into both flexible capacitor devices and indium-gallium-zinc oxide (IGZO) flexible thin-film transistors.

A plasmon-assisted fluoro-immunoassay using gold nanoparticle-decorated carbon nanotubes for monitoring the influenza virus.

A plasmon-assisted fluoro-immunoassay (PAFI) was developed for the detection of the influenza virus by using Au nanoparticle (Au NP)-decorated carbon nanotubes (AuCNTs) that were synthesized using phytochemical composites at room temperature in deionized water. Specific antibodies (Abs) against the influenza virus were conjugated onto the surface of AuCNTs and cadmium telluride quantum dots (QDs), which had a photoluminescence intensity that varied as a function of virus concentration and a detection limit of 0.1 pg/mL for all three types of influenza viruses examined. The clinically isolated influenza viruses (A/Yokohama/110/2009 (H3N2)) were detected in the range of 50-10,000 PFU/mL, with a detection limit of 50 PFU/mL. From a series of proof-of-concept and clinical experiments, the developed PAFI biosensing system provided robust signal production and enhancement, as well as an excellent selectivity and sensitivity for influenza viruses. This nanoparticle-based technique could be potentially developed as an efficient detection platform for the influenza virus.

Cytotoxicity and gene expression in sarcoma 180 cells in response to spiky magnetoplasmonic supraparticles.

Multifunctional nanoparticles (NPs) have been designed for a variety of cell imaging and therapeutic applications, and the study of their cellular interactions is crucial to the development of more efficient biomedical applications. Among current nanomaterials, concave core-shell NPs with complex angled geometries are attractive owing to their unique shape-dependent optical and physical properties as well as different tendency for cell interaction. In this study, we investigated the morphology effect of spiky gold-coated iron oxide supraparticles (Fe3O4@Au SPs) on cytotoxicity and global gene expression in sarcoma 180 cells. Cells treated for 7 days with spiky supraparticles (SPs) at concentrations up to 50 µg/mL showed >90% viability, indicating that these NPs were nontoxic. To shed light on the differences in cytotoxicity, we monitored the expression of 33,315 genes using microarray analysis of SP-treated cells. The 171 up-regulated genes and 181 down-regulated genes in spiky SP-treated cells included Il1b, Spp1, Il18, Rbp4, and Il11ra1, where these genes are mainly involved in cell proliferation, differentiation, and apoptosis. These results suggested that the spiky Fe3O4@Au SPs can induce noncytotoxicity and gene expression in tumor cells, which may be a promising cornerstone on which to base related research such as cyto-/genotoxicology of nanomaterials or the design of nanoscale drug carriers.

Formamide mediated, air-brush printable, indium-free soluble Zn-Sn-O semiconductors for thin-film transistor applications.

In this study, for high-performance indium-free metal oxide channel layer, we synthesize Zn-Sn-O (ZTO) precursor solutions in which formamide is incorporated as an additive for catalyzing the subsequent sol-gel reactions and the evolution of chemical structure. It is revealed that the formamide plays a critical chemical role in evolving a chemical structure with more oxygen-deficient oxide lattice and with less hydroxide, allowing for high field-effect mobility over 7 cm(2)/V·s. Furthermore, it is for the first time demonstrated that electrically active metal-oxide films can be patterned, using an air-brush printing technique, by directly depositing formamide-mediated ZTO-precursor solutions in patterned geometries.

CoCl2 induces apoptosis through the mitochondria- and death receptor-mediated pathway in the mouse embryonic stem cells.

Embryonic hypoxia/ischemia is a major cause of a poor fetal outcome and future neonatal and adult handicaps. However, biochemical cellular events in mouse embryonic stem (mES) cells during hypoxia remains unclear. This study investigated the underlying mechanism of apoptosis in mES cells under CoCl2-induced hypoxic/ischemic conditions. CoCl2 enhanced the expression of hypoxia-inducible factor-1α (HIF-1α) and the accumulation of reactive oxygen species in mES cells. The CoCl2-treated mES cells showed a decrease in cell viability as well as typical apoptotic changes, cell shrinkage, chromatin condensation, and nuclear fragmentation and an extended G2/M phase of the cell cycle. CoCl2 augmented the release of cytochrome c into the cytosol from the mitochondria with a concomitant loss of the mitochondrial transmembrane potential (ΔΨm) and upregulated the voltage-dependent anion channel. In addition, CoCl2-induced caspase-3, -8, and -9 activation and upregulation of p53 level, whereas downregulated Bcl-2 and Bcl-xL, a member of the anti-apoptotic Bcl-2 family in mES cells. Furthermore, CoCl2 led to the upregulation of Fas and Fas-ligand, which are the death receptor assemblies, as well as the cleavage of Bid in mES cells. These results suggest that CoCl2 induces apoptosis through both mitochondria- and death receptor-mediated pathways that are regulated by the Bcl-2 family in mES cells.