Magnetically boosted 1D photoactive microswarm for COVID-19 face mask disruption.

The recent COVID-19 pandemic has resulted in the massive discard of pandemic-related plastic wastes, causing serious ecological harm and a high societal burden. Most single-use face masks are made of synthetic plastics, thus their careless disposal poses a direct threat to wildlife as well as potential ecotoxicological effects in the form of microplastics. Here, we introduce a 1D magnetic photoactive microswarm capable of actively navigating, adhering to, and accelerating the degradation of the polypropylene microfiber of COVID-19 face masks. 1D microrobots comprise an anisotropic magnetic core (Fe3O4) and photocatalytic shell (Bi2O3/Ag), which enable wireless magnetic maneuvering and visible-light photocatalysis. The actuation of a programmed rotating magnetic field triggers a fish schooling-like 1D microswarm that allows active interfacial interactions with the microfiber network. The follow-up light illumination accelerates the disruption of the polypropylene microfiber through the photo-oxidative process as corroborated by morphological, compositional, and structural analyses. The active magnetic photocatalyst microswarm suggests an intriguing microrobotic solution to treat various plastic wastes and other environmental pollutants.

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.

Plasmonic-magnetic nanorobots for SARS-CoV-2 RNA detection through electronic readout.

The coronavirus disease 2019 (COVID-19) has prompted an urgent demand for nanotechnological solutions towards the global healthcare crisis, particularly in the field of diagnostics, vaccines, and therapeutics. As an emerging tool for nanoscience and technology, micro/nanorobots have demonstrated advanced performances, such as self-propelling, precise maneuverability, and remote actuation, thus hold great potential to provide breakthroughs in the COVID-19 pandemic. Here we show a plasmonic-magnetic nanorobot-based simple and efficient COVID-19 detection assay through an electronic readout signal. The nanorobots consist of Fe3O4 backbone and the outer surface of Ag, that rationally designed to perform magnetic-powered propulsion and navigation, concomitantly the probe nucleic acids transport and release upon the hybridization which can be quantified with the differential pulse voltammetry (DPV) technique. The magnetically actuated nanorobots swarming enables enhanced micromixing and active targeting, thereby promoting binding kinetics. Experimental results verified the enhanced sensing efficiency, with nanomolar detection limit and high selectivity. Further testing with extracted SARS-CoV-2 viral RNA samples validated the clinical applicability of the proposed assay. This strategy is versatile to extend targeting various nucleic acids, thus it could be a promising detection tool for other emerging pathogens, environmental toxins, and forensic analytes.

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.

Emission-tunable probes using terbium(III)-doped self-activated luminescent hydroxyapatite for in vitro bioimaging.

Lanthanide ion (Ln3+)-doped nanoscale hydroxyapatites (nHAp) with tunable luminescence have attracted increasing attention due to their potential applications as useful biomedical tools (e.g., imaging and clinical therapy). In this study, we reported that doping Terbium (III) ions (Tb3+) in self-activated luminescent nHAp via a facile hydrothermal reaction, using trisodium citrate (Cit3-), generates unique emission-tunable probes known as Cit/Tb-nHAp. The morphology, crystal phase, and luminescence properties of these Cit/Tb-nHAp probes are studied in detail. Moreover, the results demonstrate that the luminescence of self-activated nHAp originates from the carbon dots trapped within the nHAp crystals, in which partial energy transfer occurs from carbon dots (CDs) to Tb3+. The color tunability is successfully achieved by regulating the addition of Cit3-. Biocompatibility study indicates that when co-cultured with C6 glioma cells in vitro for 3 days, ≤800 ppm Cit/Tb-nHAp is not cytotoxic for C6 glioma cells. We also present in vitro data showing efficient cytoplasmic localization of transferrin conjugated Cit/Tb-nHAp into C6 glioma cells by fluorescence cell imaging. We have successfully engineered Cit/Tb-nHAp, a promising biocompatible agent for future in vitro and in vivo fluorescence bioimaging.

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.

Porosity-controllable magnetoplasmonic nanoparticles and their assembled arrays.

Control of the chemical and physical properties of nanoscale colloids and their nanoassemblies remains a challenging issue for enhancing the performance and functionalities of nanodevices. In this study, we report a post-synthesis etching method to tailor the porosity of the Fe3O4 shells coating on Ag NPs, establishing a facile but effective approach to regulate the chemical and optical properties of the colloids and their assembled structures. As the shell porosity increases, the NPs are transformed, producing enhanced catalytic activity and the surface-enhanced Raman spectroscopy (SERS) effect, which results from enhanced chemical diffusion into the Ag core. Magnetoplasmonic (MagPlas) one- (1D) and two- (2D) dimensional arrays fabricated using these porosity-controllable NPs exhibit intriguing plasmon properties that are strongly affected by the porosity of the particle shell. Furthermore, the bright coloration of the 2D arrays is tuned by changing the shell porosity or introducing an additional metallic layer. Such 1D and 2D porous MagPlas metastructures possessing Fe3O4 shells with tunable porosities are a fulcrum for developing recyclable catalysts and tunable optical filters with optimized activity, selectivity, and sensitivity, as well as color displays and sensing platforms.

Magnetic Layer-by-Layer Assembly: From Linear Plasmonic Polymers to Oligomers.

One-dimensional nanostructures with controllable aspect ratios are essential for a wide range of applications. An approach for magnetic superparticle (SP) assembly over large areas (55 mm × 25 mm) is introduced via co-assistance of electrostatic and magnetic fields, so-called magnetic layer-by-layer assembly, on an arbitrary hydrophilic substrate within minutes. The SP structures [diameter (d) = 120-350 nm] of Fe3O4 or Ag@Fe3O4 composites composed of hundreds of magnetite nanocrystals (d = 10-20 nm) are used as colloidal monomers to fabricate arrays of high aspect ratio (up to 102) linear nanochains, viz. colloidal polymers, where thermal disturbances were minimized. The arrays of colloidal polymers exhibit strong optical polarization effects owing to their geometrical anisotropy, which can be used as a simple optical filter. Furthermore, by using the binary colloidal mixture of different magnetic colloids, including different sized Fe3O4 and magnetoplasmonic Ag@Fe3O4, low aspect ratio (2-15) colloidal chains, viz. magnetic/plasmonic oligomers, with tunable lengths were fabricated, affording a facile but an effective approach to modulate the optical properties of the chains. The scalable fabrication of well-aligned, linear colloidal polymers and oligomers opens up appealing opportunities for the development of sensors, subwavelength waveguides, optical tweezers, and enhanced solar harvesting devices.

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.

Real-time SPR imaging based on a large area beam from a wavelength-swept laser.

We demonstrate a real-time surface plasmon resonance imaging (SPRi) system based on a wavelength-swept laser. Compared to conventional spectral-modulation SPRi using white light source and spectral filtering, the proposed system has a higher scan rate to detect rapid changes in refractive index and a higher output power for large-area illumination. This SPRi system achieves scan rates faster than 12 Hz, simultaneously obtaining SPR dip positions over full illumination fields of 12×12 mm. Using the wavelength-swept laser, two-dimensional biomolecular array imaging can be acquired with a high dynamic detection range (7.67×10-3 refractive index unit (RIU)) as well as high sensitivity (6501 nm/RIU) and resolution (1.89×10-6 RIU).

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.

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.

RGD peptide and graphene oxide co-functionalized PLGA nanofiber scaffolds for vascular tissue engineering.

In recent years, much research has been suggested and examined for the development of tissue engineering scaffolds to promote cellular behaviors. In our study, RGD peptide and graphene oxide (GO) co-functionalized poly(lactide-co-glycolide, PLGA) (RGD-GO-PLGA) nanofiber mats were fabricated via electrospinning, and their physicochemical and thermal properties were characterized to explore their potential as biofunctional scaffolds for vascular tissue engineering. Scanning electron microscopy images revealed that the RGD-GO-PLGA nanofiber mats were readily fabricated and composed of random-oriented electrospun nanofibers with average diameter of 558 nm. The successful co-functionalization of RGD peptide and GO into the PLGA nanofibers was confirmed by Fourier-transform infrared spectroscopic analysis. Moreover, the surface hydrophilicity of the nanofiber mats was markedly increased by co-functionalizing with RGD peptide and GO. It was found that the mats were thermally stable under the cell culture condition. Furthermore, the initial attachment and proliferation of primarily cultured vascular smooth muscle cells (VSMCs) on the RGD-GO-PLGA nanofiber mats were evaluated. It was revealed that the RGD-GO-PLGA nanofiber mats can effectively promote the growth of VSMCs. In conclusion, our findings suggest that the RGD-GO-PLGA nanofiber mats can be promising candidates for tissue engineering scaffolds effective for the regeneration of vascular smooth muscle.

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..

Early detection of the growth of Mycobacterium tuberculosis using magnetophoretic immunoassay in liquid culture.

Tuberculosis (TB) is an often neglected, epidemic disease that remains to be controlled by contemporary techniques of medicine and biotechnology. In this study, a nanoscale sensing system, referred to as magnetophoretic immunoassay (MPI) was designed to capture culture filtrate protein (CFP)-10 antigens effectively using two different types of nanoparticles (NPs). Two specific monoclonal antibodies against CFP-10 antigen were used, including gold NPs for signaling and magnetic particles for separation. These results were carefully compared with those obtained using the commercial mycobacteria growth indicator tube (MGIT) test via 2 sequential clinical tests (with ca. 260 clinical samples). The sensing linearity of MPI was shown in the range of pico- to micromoles and the detection limit was 0.3pM. MPI using clinical samples shows robust and reliable sensing while monitoring Mycobacterium tuberculosis (MTB) growth with monitoring time 3-10 days) comparable to that with the MGIT test. Furthermore, MPI distinguished false-positive samples from MGIT-positive samples, probably containing non-tuberculous mycobacteria. Thus, MPI shows promise in early TB diagnosis.

Preparation of concave magnetoplasmonic core-shell supraparticles of gold-coated iron oxide via ion-reducible layer-by-layer method for surface enhanced Raman scattering.

Preparation of suprastructure assemblies with unique colloidal and optical properties remains challenging. Non-uniform covering of magnetic nanoparticles (NPs) with an external inert Au shell has been attempted to protect the magnetic core against oxidation as well as to produce multifunctional supraparticles (SPs) possessing respective optical and magnetic properties. In this study, a concave Au NP coating was deposited on magnetic nanoparticles (MNPs) with precise control of the shell thickness and roughness through a layer-by-layer (LbL) assisted ionic reduction method termed ion-reducible LbL (IR-LbL) method. Surface enhanced Raman spectra were obtained using graphene quantum dots (GQDs) on the magnetically aligned structure of the prepared core-shell SPs. It is probable that this synthesis method and the generated SPs are essential for characterizing the merge of electronics and magnetism in the nano-regime and may be applicable for further electronics, magnetic storage, and biomedical applications.

In situ self-assembly of gold nanoparticles on hydrophilic and hydrophobic substrates for influenza virus-sensing platform.

Nanomaterials without chemical linkers or physical interactions that reside on a two-dimensional surface are attractive because of their electronic, optical and catalytic properties. An in situ method has been developed to fabricate gold nanoparticle (Au NP) films on different substrates, regardless of whether they are hydrophilic or hydrophobic surfaces, including glass, 96-well polystyrene plates, and polydimethylsiloxane (PDMS). A mixture of sodium formate (HCOONa) and chloroauric acid (HAuCl4) solution was used to prepare Au NP films at room temperature. An experimental study of the mechanism revealed that film formation is dependent on surface wettability and inter particle attraction. The as-fabricated Au NP films were further applied to the colorimetric detection of influenza virus. The response to the commercial target, New Caledonia/H1N1/1999 influenza virus, was linear in the range from 10 pg/ml to 10 µg/ml and limit of detection was 50.5 pg/ml. In the presence of clinically isolated influenza A virus (H3N2), the optical density of developed color was dependent on the virus concentration (10-50,000 PFU/ml). The limit of detection of this study was 24.3 PFU/ml, a limit 116 times lower than that of conventional ELISA (2824.3 PFU/ml). The sensitivity was also 500 times greater than that of commercial immunochromatography kits.

Cancer upregulated gene 2 induces epithelial-mesenchymal transition of human lung cancer cells via TGF-ß signaling.

Cancer upregulated gene 2 (CUG2) enhances cell migration and invasion, but the underlying mechanism has not been revealed. Herein, CUG2 decreased the expression of E-cadherin and increased the expression of N-cadherin and vimentin, characteristics of the epithelial-mesenchymal transition (EMT). A CUG2 deletion mutant, lacking interaction with nucleophosmin 1 (NPM1), or suppression of NPM1 reduced wound healing and cell invasion, indicating that CUG2-mediated EMT requires NPM1. CUG2 enhanced activation of Smad2/3 and expression of Snail and Twist, while the CUG2 silence decreased these TGF-ß signaling pathways, leading to suppression of EMT. NPM silence also inhibited the CUG2-induced TGF-ß signaling. These results suggest that TGF-ß signaling is involved in CUG2-induced EMT. Treatment with EW-7197, a novel inhibitor of TGF-ß signaling, diminished CUG2-mediated EMT and inhibition of Akt, ERK, JNK, and p38 MAPK, non-canonical TGF-ß signaling molecules, also decreased expression of Smad2/3, Snail and Twist, leading to inhibition of EMT. The results confirm that TGF-ß signaling is essential for CUG2-mediated EMT. Interestingly, TGF-ß enhanced CUG2 expression. We further found that both CUG2-induced TGF-ß production and TGF-ß-induced CUG2 up-regulation required a physical interaction between Sp1 and Smad2/3 in the CUG2 and TGF-ß promoter, as demonstrated by a promoter reporter assay, immunoprecipitation, and ChIP assay. These results indicated close crosstalk between CUG2 and TGF-ß. Conversely, suppression of CUG2 or NPM1 did not completely inhibit TGF-ß-induced EMT, indicating that the effect of TGF-ß on EMT is dominant over the effect of CUG2 on EMT. Collectively, our findings suggest that CUG2 induces the EMT via TGF-ß signaling.