Layer-by-layer assembly of quercetin-loaded zein/γPGA/low-molecular-weight chitosan/fucoidan nanosystem for targeting inflamed blood vessels.

Chitosan acts as a versatile carrier in polymeric nanoparticle (NP) for diverse drug administration routes. Delivery of antioxidants, such as quercetin (Qu) showcases potent antioxidant and anti-inflammatory properties for reduction of various cardiovascular diseases, but low water solubility limits uptake. To address this, we developed a novel layer-by-layer zein/gamma-polyglutamic acid (γPGA)/low-molecular-weight chitosan (LC)/fucoidan NP for encapsulating Qu and targeting inflamed vessel endothelial cells. We used zein (Z) and γPGA (r) to encapsulate Qu (Qu-Zr NP) exhibited notably higher encapsulation efficiency compared to zein alone. Qu-Zr NP coated with LC (Qu-ZrLC2 NP) shows a lower particle size (193.2 ± 2.9 nm), and a higher zeta potential value (35.2 ± 0.4 mV) by zeta potential and transmission electron microscopy analysis. After coating Qu-ZrLC2 NP with fucoidan, Qu-ZrLC2Fa NP presented particle size (225.16 ± 0.92 nm), zeta potential (-25.66 ± 0.51 mV) and maintained antioxidant activity. Further analysis revealed that Qu-ZrLC2Fa NP were targeted and taken up by HUVEC cells and EA.hy926 endothelial cells. Notably, we observed Qu-ZrLC2Fa NP targeting zebrafish vessels and isoproterenol-induced inflamed vessels of rat. Our layer-by-layer formulated zein/γPGA/LC/fucoidan NP show promise as a targeted delivery system for water-insoluble drugs. Qu-ZrLC2Fa NP exhibit potential as an anti-inflammatory therapeutic for blood vessels.

Biological cell trapping and manipulation of a photonic nanojet by a specific microcone-shaped optical fiber tip.

Trapping and manipulating mesoscopic biological cells with high precision and flexibility are very important for numerous biomedical applications. In particular, a photonic nanojet based on a non-resonance focusing phenomenon can serve as a powerful tool for manipulating red blood cells and tumor cells in blood. In this study, we demonstrate an approach to trap and drive cells using a high-quality photonic nanojet which is produced by a specific microcone-shaped optical-fiber tip. The dynamic chemical etching method is used to fabricate optical-fiber probes with a microcone-shaped tip. Optical forces and potentials exerted on a red blood cell by a microcone-shaped fiber tips are analyzed based on finite-difference time-domain calculations. Optical trapping and driving experiments are done using breast cancer cells and red blood cells. Furthermore, a cell chain is formed by adjusting the magnitude of the optical force. The real-time backscattering intensities of multiple cells are detected, and highly sensitive trapping is achieved. This microcone-shaped optical fiber probe is potentially a powerful device for dynamic cell assembly, optical sorting, and the precise diagnosis of vascular diseases.

A low-molecular-weight chitosan fluorometric-based assay for evaluating antiangiogenic drugs.

Low-molecular-weight chitosan (LMWCS) damaged cell membranes in zebrafish showed its possibility to release reporter proteins for detection. In this study, we developed a simple fluorometric-based assay for the evaluation of clinical antiangiogenic drugs using LMWCS and Tg(fli1:EGFP) transgenic zebrafish, which expressed green-fluorescence protein (GFP) in the endothelial cells of blood vessel. In vitro stable and transiently transfected cell lines was released luciferase and green fluorescent protein (GFP) for intensity evaluation upon LMWCS fluorometric-based assay. In vivo Tg(fli1:EGFP) transgenic zebrafish was also released GFP from endothelial cells of blood vessels and show an increase of fluorescent intensity upon LMWCS fluorometric-based assay. Treatment with the clinical antiangiogenic drug sorafenib and analyzed by LMWCS fluorometric-based assay showed significantly reduction of angiogenesis. Furthermore, treatment with 2 µM sorafenib showed a significant reduction in angiogenesis of the intersegmental vein (ISV) and dorsal longitudinal anastomotic vessels (DLAV) in Tg(fli1:EGFP) transgenic zebrafish. Fluorescence intensity reduction from 2 µM sorafenib was used as a factor in the LMWCS fluorescence-based assay for relative antiangiogenic evaluation. Relative angiogenesis evaluation of the clinical drugs axitinib, cabozantinib, and regorafenib showed a significant reduction. Collectively, this study provided a simple, convenient, and rapid LMWCS fluorometric-based assay for evaluating angiogenic drugs using transgenic zebrafish.

Magnetic Concentric Hot-Circle Generation at Optical Frequencies in All-Dielectric Mesoscale Janus Particles.

The development of all-dielectric structures with high magnetic response at optical frequencies has become a matter of intense study in past years. However, magnetic effects are weak at optical frequencies due to the small value of the magnetic permeability of natural materials. To this end, natural dielectric materials are unemployable for practical "magnetic" applications in optics. We have shown for the first time that it is possible to induce intense magnetic concentric subwavelength "hot circles" in a dielectric mesoscale Janus particle. The basis of the Janus particle is a combination of the effects of a photonic jet, whispering-gallery waves, and the concept of solid immersion. Simulations show an (H/H0)2/(E/E0)2 contrast of more than 10, and maximal magnetic field intensity enhancement is more than 1000 for a wavelength-scaled particle with a refractive index n < 2 and a size parameter in the order of 30. This work may provide a new way to realize precise magnetic devices for integrated photonic circuits and light−matter interaction.

Biocompatible spider silk-based metal-dielectric fiber optic sugar sensor.

Various optical components employed in biomedical applications have been fabricated using spider silk because of its superior properties, such as elasticity, tensile strength, biodegradability, and biocompatibility. In this study, a highly sensitive fiber optic sugar sensor is fabricated using metal-nanolayer-coated spider silk. The spider silk, which is directly collected from Nephila pilipes, a giant wood spider, is naturally a protein-based biopolymer with great flexibility, low attenuation, and easy functionalization. The surface of the spider silk-based fiber is coated with a metal nano-layer by using the glancing angle deposition technique. This fiber optic sugar sensor is based on the principle of the change in the refractive indices of sugar solutions. The attained experimental results show that the proposed sugar sensor is highly sensitive in the detection of fructose, sucrose, and glucose concentrations. This work may provide a new way to realize precise and sensitive online sugar measurements for point-of-care diagnostics.

Corrigendum: The cholesterol-binding sequence in monomeric C-reactive protein binds to the SARS-CoV-2 spike receptor-binding domain and blocks interaction with Angiotensin-converting enzyme 2.

[This corrects the article DOI: 10.3389/fimmu.2022.918731.].

The Cholesterol-Binding Sequence in Monomeric C-Reactive Protein Binds to the SARS-CoV-2 Spike Receptor-Binding Domain and Blocks Interaction With Angiotensin-Converting Enzyme 2.

The receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the human angiotensin-converting enzyme 2 (ACE2) receptor, which is a prerequisite for the virus to enter the cell. C-reactive protein (CRP) is an important marker of inflammation and is a putative soluble pattern recognition receptor. Clinical elevation of CRP levels in patients with COVID-19 is one of the characteristics of the disease; however, whether CRP is involved in COVID-19 pathogenesis is unknown. Here, we report that monomeric CRP (mCRP) can bind to the SARS-CoV-2 spike RBD and competitively inhibit its binding to ACE2. Furthermore, truncated mutant peptide competition assays and surface plasmon resonance binding experiments showed that the cholesterol-binding sequence (CBS, amino acids 35-47) in mCRP was critical for mediating the binding of mCRP to spike RBD. In a cell model of spike RBD and ACE2 interaction, the CBS motif effectively reduced the binding of spike RBD to ACE2 overexpressed on the cell surface. Thus, this study highlights the pattern recognition function of mCRP in innate immunity and provides a preliminary theoretical basis for the development of the CBS motif in mCRP into a functional peptide with both diagnostic significance and potential therapeutic capabilities.

In-plane subwavelength optical capsule for lab-on-a-chip nano-tweezers.

In this Letter, we propose a new, to the best of our knowledge, proof-of-concept of optical nano-tweezers based on a pair of dielectric rectangular structures that are capable of generating a finite-volume in-plane optical capsule. Finite-difference time-domain simulations of light spatial distributions and optical trapping forces of a gold nanoparticle immersed in water demonstrate the physical concept of an in-plane subwavelength optical capsule integrated with a microfluidic mesoscale device. It is shown that the refractive index of and the distance between the two dielectric rectangular structures can effectively control the shape and axial position of the optical capsule. Such an in-plane mesoscale structure provides a new path for manipulating absorbing nano-particles or bio-particles in a compact planar architecture, and should thus lead to promising perspectives in lab-on-a-chip domains.

A novel low-molecular-weight chitosan/gamma-polyglutamic acid polyplexes for nucleic acid delivery into zebrafish larvae.

Many challenges, such as virus infection, extreme weather and long cultivation periods, during the development of fish larvae have been observed, especially in aquaculture. Gene delivery is a useful method to express functional genes to defend against these challengers. However, the methods for fish larvae are insufficient. In our earlier report, low-molecular-weight chitosan (LMWCS) showed a strong positive charge and may be useful for polyplex formulation. Herein, we present a simple self-assembly of LMWCS polyplexes (LMWCSrNPs) for gene delivery into zebrafish larvae. Different weight ratios of LMWCS/gamma-polyglutamic acid (γ-PGA)/plasmid DNA were analyzed by gel mobility assay. Delivery efficiency determined by green fluorescent protein (GFP) expression in zebrafish liver (ZFL) cells showed that delivery efficiency at a weight ratio of 20:8:1 was higher than others. Zeta potential and transmission electron microscopy (TEM) analysis showed that the round shape of the particle size varied. In our earlier reports, IRF9S2C could induce interferon-stimulated gene (ISG) expression to induce innate immunity in zebrafish and pufferfish. Further delivery of pcDNA3-IRF9S2C-HA plasmid DNA into ZFL cells and zebrafish larvae by LMWCSrNP successfully induced ISG expression. Collectively, LMWCSrNP could be a novel gene delivery system for zebrafish larvae and might be used to improve applications in aquaculture.

Diffraction limited photonic hook via scattering and diffraction of dual-dielectric structures.

Photonic hooks have demonstrated to be great candidates for multiple applications ranging from sensing up to optical trapping. In this work, we propose a mechanism to produce such bent structured light beams by exploiting the diffraction and scattering generated by a pair of dielectric rectangles immersed in free space. It is shown how the photonic hooks are generated away from the output surface of the dielectrics by correctly engineering each individual dielectric structure to generate minimum diffraction and maximum scattering along the propagation axis. Different scenarios are studied such as dual-dielectric structures having different lateral dimensions and refractive index as well as cases when both dielectrics have the same lateral dimensions. The results are evaluated both numerically and theoretically demonstrating an excellent agreement between them. These results may open new avenues for optical trapping, focusing and sensing devices via compact and simple dual-dielectric structures.

Simulation and experimental observations of axial position control of a photonic nanojet by a dielectric cube with a metal screen.

In this Letter, we report on a numerical study, fabrication, and experimental observations of photonic nanojet (PNJ) shaping by control of a tangential electric field component. Here the PNJs are generated by a single mesoscale micro-cube that is fabricated from polydimethylsiloxane, deposited on a silicon substrate and placed on thick metal screen at illuminating wavelengths of 405, 532, and 671 nm. It is shown that the length, focal length, and width of the PNJ can be significantly reduced in the presence of the metal masks along the side faces of the micro-cube. Experimental measurements of the PNJ imaging are performed by a scanning optical microscope with laser sources. Our experimental results are in reasonable agreement with simulation predictions of the finite-difference time-domain method. Due to the appearance of the metal masks, the PNJ focal length decreases 1.5 times, the PNJ decay length decreases 1.7 times, and the PNJ resolution increases 1.2 times. Such PNJs possess great potential in complex manipulation, including integrated plasmonic circuits, biosensing, and optical tweezers.

Islet transplantation ameliorates diabetes-induced testicular interstitial fibrosis and is associated with inhibition of TGF-ß1/Smad2 pathway in a rat model of type 1 diabetes.

Islet transplantation (IT) is considered the most effective endocrine replacement therapy for diabetes mellitus (DM). Studies have demonstrated that IT can repair testicular structural injury caused by inflammatory and oxidative stress in a diabetic rat model. However, highly effective exogenous antioxidant and anti-inflammatory drugs can achieve this effect. Testicular interstitial fibrosis caused by long-term hyperglycemia is however difficult to reverse or recover. Thus far, there are no effective drugs that prevent or relieve testicular interstitial fibrosis. Therefore, it is necessary to explore the potential benefit of IT on testicular interstitial fibrosis induced by DM and its underlying molecular mechanisms. In the present study, Wistar rats were used to establish a DM model by intraperitoneal injection of streptozotocin. The diabetic models then underwent IT or received insulin treatment after 12 weeks. IT was more effective than insulin treatment in ameliorating diabetic-induced testicular interstitial fibrosis, Leydig cells apoptosis, testosterone deficiency and poor sperm motility. IT and insulin treatment both significantly inhibited the upregulation of TGF-ß1 and phosphorylated Smad2 in DM, with IT being more effective than insulin. The present study's findings proved that IT effectively protects diabetic-induced testicular interstitial fibrosis probably by inhibiting the TGF-ß1/Smad2 signaling pathway, which offers hope in male patients with DM complicating with testicular interstitial fibrosis.

Concept of photonic hook scalpel generated by shaped fiber tip with asymmetric radiation.

Structured light have made deep impacts on modern biotechnology and clinical practice, with numerous optical systems and lasers currently being used in medicine to treat disease. We demonstrate a new concept of fiber-based optical hook scalpel. The subwavelength photonic hook is obtained in the vicinity of a shaped fiber tip with asymmetric radiation. A 1550 nm continuous-wave source, commonly used for medical imaging, has been required. Photonic hook with a lateral feature size less than the half-wavelength is achieved using a hemispherical shaped fiber tip with metallic mask. This breakthrough is carried out in ambient air by using a 4-µm-diameter fiber with a shaped tip. A good correlation is observed between the computed intensity distribution of photonic hook and the tip sizes. Photonic hook generated with a shaped fiber tip, easier to manipulate, shows far-reaching benefits for potential applications such as ophthalmic laser surgery, super-resolution microscopy, photolithography and material processing.

Experimental demonstration of a tunable photonic hook by a partially illuminated dielectric microcylinder.

In this Letter, we report the experimental observations of a tunable curved photonic nanojet (photonic hook) generated by a 5 µm polydimethylsiloxane microcylinder deposited on a silicon substrate and illuminated by 405 nm laser beam. A moveable opaque aluminum-mask is mounted in front of the microcylinder implementing partial illumination and imparting spatial curvature to the photonic nanojet. Experimental results of main parameters (tilt angle, width, and intensity) of emerging photonic hooks exhibit close agreement with numerical predictions of the near-field optical structures. The experimentally measured full widths at half-maximum of photonic hooks are 0.48λ, 0.56λ, and 0.76λ for tilt angles of θ=0∘, 5.7°, and 20.1°, respectively. Photonic hooks possess great potential in complex manipulation such as super-resolution imaging, surface fabrication, and optomechanical manipulation along curved trajectories.

Experimental observation of flat focusing mirror based on photonic jet effect.

In this work, we experimentally demonstrate that a thin rectangle dielectric-metal structure can have a function of a flat focusing mirror based on photonic jet effect in reflection mode. Using polydimethylsiloxane (PDMS) rectangle with size length of 10 µm and wavelength-scale thickness of 1 µm on the top of a silicon wafer, we have built a flat mirror which focuses an incident beam at the focal length changing from 1.38 µm to 11.67 µm upon tuning the beam incidence angle from 30° to 75°. The focusing properties of such a mirror persist in the wavelength range of 405 nm to 671 nm. Our approach can be extended to realize other optical functionalities by properly controlling rectangle dimensions and materials. This flat focusing mirror is able to guide the incident beam in free space without perceptible diffraction at the distance equal to the photonic jet length and suitable for small-scale photonic circuits.

Experimental verification of twin photonic nanojets from a dielectric microcylinder.

In this Letter, the direct generation of twin photonic nanojets (PNJs) through two coherent illuminations of a microcylinder is investigated theoretically and experimentally. The dielectric microcylinder (polydimethylsiloxane) with 5 µm diameter and 6 µm height is employed to generate symmetric twin PNJs. The finite-difference time-domain calculation is used to simulate the electric field distributions inside and outside the microcylinder. The scanning optical microscope system is performed for experimental verification of twin photonic nanojets. In both theory and in practice, the intensity null of electric field creates two separate PNJs. Compared to a single PNJ, twin PNJs have a smaller subwavelength waist and more complex intensity distribution. The focal distance, interval, and full width at half-maximum of twin PNJs are a function of the offset angle. The twin PNJs will provide novel applications in nanolithography, optical trapping, biophotonic sensing, and therapy.

Formation of high-quality photonic nanojets by decorating spider silk.

The photonic nanojet is a highly concentrated beam with low divergence on the shadow side of dielectric microparticles. In this Letter, we first theoretically and experimentally investigate the formation of high-quality photonic nanojets by decorating spider silk. The dragline silks are directly extracted from cellar spiders and capable of efficiently collecting ultraviolet cure adhesive. The liquid-collecting capacity of the captured silk is the result of a singular fiber structure with periodic spindle knots. Using a scanning-optical-microscope system, we show that high-quality photonic nanojets are generated by silk fiber with spindle knots. With the variation in spindle-knot dimensions, the properties of photonic nanojets, such as intensity distribution, focal length, and full width at half-maximum, are able to tune flexibly. By combining the unique biocompatibility, flexibility, and tensile strength, the silk filaments with spindle knots pave a potential way for original bio-photonic applications.

Primitive chain network simulations of probe rheology.

Probe rheology experiments, in which the dynamics of a small amount of probe chains dissolved in immobile matrix chains is discussed, have been performed for the development of molecular theories for entangled polymer dynamics. Although probe chain dynamics in probe rheology is considered hypothetically as single chain dynamics in fixed tube-shaped confinement, it has not been fully elucidated. For instance, the end-to-end relaxation of probe chains is slower than that for monodisperse melts, unlike the conventional molecular theories. In this study, the viscoelastic and dielectric relaxations of probe chains were calculated by primitive chain network simulations. The simulations semi-quantitatively reproduced the dielectric relaxation, which reflects the effect of constraint release on the end-to-end relaxation. Fair agreement was also obtained for the viscoelastic relaxation time. However, the viscoelastic relaxation intensity was underestimated, possibly due to some flaws in the model for the inter-chain cross-correlations between probe and matrix chains.

Direct imaging of optimal photonic nanojets from core-shell microcylinders.

We first experimentally evaluate the direct imaging of photonic nanojets from core-shell microcylinders. The optimal photonic nanojet with long length, a high intensity spot, and low divergence is observed at the designed gold-silver-coating microcylinder. A special microcylinder consists of multilayered metallic shells (gold, silver, and copper) and a dielectric core (polydimethylsiloxane) at a diameter of 5 µm and a height of 6 µm. The electromagnetic distributions inside and outside the core-shell microcylinders are calculated by using the finite-difference time-domain method. The direct-imaging measurements for photonic nanojets are performed with a scanning-optical-microscope system. Such core-shell microcylinders provide new pathways for high-resolution optical imaging, which are useful for biophotonics, plasmonics, and optical data storage.

Photonic jets produced by dielectric micro cuboids.

The formation of photonic jets produced by dielectric micro cuboids is reported. The spatial electromagnetic field has been numerically analyzed on the basis of the finite-difference time-domain calculation. The characteristics of photonic jets, such as propagation length and location, can be drastically changed by controlling the cuboid dimensions. Visually three morphological types of photonic jets are introduced for classification. Combining key parameters of photonic jets, the quality criterion is used to describe the jet quality. The super resolution imaging of the dielectric micro cuboid can be expected from the long focal length and small beam waist. The simulation results show that it can be of interest for several potential applications, such as subdiffraction resolution optical microlenses, ultradirectional optical antennae, and nanolithography based on the micro cuboid.