Folic acid functionalized gadolinium-doped carbon dots as fluorescence / magnetic resonance imaging contrast agent for targeted imaging of liver cancer.

Gadolinium-doped carbon dots (Gd-CDs), as a new class of nanomaterial, has a wide application prospect in targeted imaging and monitoring diagnosis and treatment of liver cancer because of their good fluorescence (FL)-magnetic resonance (MR) imaging properties. First, Gd-CDs were synthesized by hydrothermal method with gadodiamide as gadolinium source, citric acid as carbon source and silane coupling agent (KH-792) as coupling agent with FL quantum yield (QY) of 48.2%. Then, folic acid (FA), which is highly expressed in liver cancer, was used as a targeting component to modify Gd-CDs to obtain targeted imaging agent (Gd-CDs-FA). The results showed that Gd-CDs and Gd-CDs-FA have low cytotoxicity and good biocompatibility, and the targeting and selectivity of Gd-CDs-FA to HepG2 cells could be observed under confocal laser scanning microscope (CLSM). The T1 longitudinal relaxation rates (r1) of Gd-CDs and Gd-CDs-FA are 15.92 mM-1s-1 and 13.56 mM-1s-1, respectively. They showed good MR imaging ability in vitro and in vivo, and MR imaging in nude mice further proved the targeting imaging performance of Gd-CDs-FA. Therefore, Gd-CDs-FA with higher QY showed good FL-MR targeting imaging ability of liver cancer, which broke through the limitations of single molecular imaging probe in sensitivity and soft tissue resolution. This study provides a new idea for the application of Gd-CDs in FL and MR targeting imaging of liver cancer.

Chiral Plasmonic Shells: High-Performance Metamaterials for Sensitive Chiral Biomolecule Detection.

Low-cost and large-area chiral metamaterials (CMs) are highly desirable for practical applications in chiral biosensors, nanophotonic chiral emitters, and beyond. A promising fabrication method takes advantage of self-assembled colloidal particles, onto which metal patches with defined orientation are created using glancing angle deposition (GLAD). However, using this method to make uniform and well-defined CMs over macroscopic areas is challenging. Here, we fabricate a uniform large-area colloidal particle array by interface-mediated self-assembly and precisely control the structural handedness of chiral plasmonic shells (CPSs) using GLAD. Strong chiroptical signals arise from twisted currents at the main, corner, and edge of CPSs, allowing a balance between strong chiroptical and high transmittance properties. Our shell-like chiral geometry shows excellent sensor performance in detecting chiral molecules due to the formation of uniform superchiral fields. Systematic investigations optimize the interplay between peak and null point resonances in different CPSs and result in a record consistency chiral sensor parameter U, i.e., 3.77 for null points and 0.0867 for peaks, which are about 54 and 1.257 times larger than the highest value (0.068) of previously reported CMs. The geometrical chirality, surface plasmonic resonance, chiral surface lattice resonance, and chiral sensor performance evidence the chiroptical effect and the excellent chiral sensor performance.

Engineering a strong and stable ultraviolet chiroptical effect in a large-area chiral plasmonic shell.

Ultraviolet chiral metamaterials (UCM) are highly desired for their strong interaction with the intrinsic resonance of molecules and ability in manipulating the polarization state of high energy photons, but rarely reported to date due to their small feature size and complex geometry. Herein, we design and fabricate a kind of novel ultraviolet chiral plasmonic shell (UCPS) by combing the stepwise Al deposition and colloid-sphere assembled techniques. The cancellation effect originated from the disorder lattices of micro-domains in the colloid monolayer has been successfully overcome by optimizing the deposition parameters, and a strong CD signal of larger than 1 deg in the UV region is demonstrated both in simulation and experiment. This strong ultraviolet chiroptical resonances mainly come from the surface chiral lattice resonance mode, the whispering gallery mode and also the interaction between neighbor shells, and can be effectively tuned by changing structural parameters, for example, the sphere diameter, or even slightly increasing the deposition temperature in experiment. To improve the stability, the fabricated UCPSs are protected by N2 in the deposition chamber and then passivated by UV-ozone immediately after each deposition step. The formed UCPS show an excellent stability when exposing in the atmospheric environment. The computer-aided geometrical model, electromagnetic modes, and the tunable chiroptical resonance modes have been systematically investigated.

Optical differentiation based on weak measurements.

Optical differentiation shows much potential to be applied in computation due to its strong parallelizability. Currently, each optical differential method can only obtain partial differential information. Here, we propose a general approach to obtain complete differentiation. Compared to previous methods, we can separately obtain the differentiation of amplitude and phase, reserve the negative value of the differentiation, and acquire the differentiation in arbitrary directions of the two-dimensional field. We measure the differentiation of the Gaussian beam to demonstrate this method. A practical experiment of identifying the move direction of the motion-blurred image is also presented to verify the practicability of our method. Our method can further be applied to intelligence algorithms, image identification, and optical analog computing.

Dual-task convolutional neural network based on the combination of the U-Net and a diffraction propagation model for phase hologram design with suppressed speckle noise.

In this paper, a dual-task convolutional neural network based on the combination of the U-Net and a diffraction propagation model is proposed for the design of phase holograms to suppress speckle noise of the reconstructed images. By introducing a Fresnel transmission layer, based on angular spectrum diffraction theory, as the diffraction propagation model and incorporating it into U-Net as the output layer, the proposed neural network model can describe the actual physical process of holographic imaging, and the distributions of both the light amplitude and phase can be generated. Afterwards, by respectively using the Pearson correlation coefficient (PCC) as the loss function to modulate the distribution of the amplitude, and a proposed target-weighted standard deviation (TWSD) as the loss function to limit the randomness and arbitrariness of the reconstructed phase distribution, the dual tasks of the amplitude reconstruction and phase smoothing are jointly solved, and thus the phase hologram that can produce high quality image without speckle is obtained. Both simulations and optical experiments are carried out to confirm the feasibility and effectiveness of the proposed method. Furthermore, the depth of field (DOF) of the image using the proposed method is much larger than that of using the traditional Gerchberg-Saxton (GS) algorithm due to the smoothness of the reconstructed phase distribution, which is also verified in the experiments. This study provides a new phase hologram design approach and shows the potential of neural networks in the field of the holographic imaging and more.

Preparation, Properties, and Application of Graphene-Based Materials in Tissue Engineering Scaffolds.

Tissue engineering has a great application prospect as an effective treatment for tissue and organ injury, functional reduction, or loss. Bioactive tissues are reconstructed and damaged organs are repaired by the three elements, including cells, scaffold materials, and growth factors. Graphene-based composites can be used as reinforcing auxiliary materials for tissue scaffold preparation because of their large specific surface area, and good mechanical support. Tissue engineering scaffolds with graphene-based composites have been widely studied. Part of research have focused on the application of graphene-based composites in single tissue engineering. The basic principles of graphene materials used in tissue engineering are summarized in some research. Some studies emphasized the key problems and solutions urgently needed to be solved in the development of tissue engineering and discussed their application prospect. Some related studies mainly focused on the conductivity of graphene and discussed the application of electroactive scaffolds in tissue engineering. In this review, the composite materials for preparing tissue engineering scaffolds are briefly described, which emphasizes the preparation methods, biological properties, and practical applications of graphene-based composite scaffolds. The synthetic techniques, with stressing solvent casting, electrospinning, and three-dimensional printing, are introduced in detail. The mechanical, cell-oriented, and biocompatible properties of graphene-based composite scaffolds in tissue engineering are analyzed and summarized. Their applications in bone tissue engineering, nerve tissue engineering, cardiovascular tissue engineering, and other tissue engineering are summarized systematically. In addition, this work also looks forward to the difficulties and challenges in the future research, providing some references for the follow-up research of graphene-based composites in tissue engineering scaffolds. Impact statement Regeneration and repair of tissue and organ injury has become a new research hotspot in recent years. Tissue engineering scaffolds prepared with graphene-based materials have good biocompatibility, excellent mechanical properties, and strong cell orientation, which can fully induce the proliferation and differentiation of seed cells. This review briefly describes the basic materials for the preparation of tissue engineering scaffolds, and focuses on the preparation, performance, and application of graphene-based materials in tissue engineering, providing sufficient understanding of graphene applied in regenerative medicine.

Research Progress in the Synthesis of Targeting Organelle Carbon Dots and Their Applications in Cancer Diagnosis and Treatment.

With increasing knowledge about diseases at the histological, cytological to sub-organelle level, targeting organelle therapy has gradually been envisioned as an approach to overcome the shortcomings of poor specificity and multiple toxic side effects on tissues and cell-level treatments using the currently available therapy. Organelle carbon dots (CDs) are a class of functionalized CDs that can target organelles. CDs can be prepared by a "synchronous in situ synthesis method" and "asynchronous modification method." The superior optical properties and good biocompatibility of CDs can be preserved, and they can be used as targeting particles to carry drugs into cells while reducing leakage during transport. Given the excellent organelle fluorescence imaging properties, targeting organelle CDs can be used to monitor the physiological metabolism of organelles and progression of human diseases, which will provide advanced understanding and accurate diagnosis and targeted treatment of cancers. This study reviews the methods used for preparation of targeting organelle CDs, mechanisms of accurate diagnosis and targeted treatment of cancer, as well as their application in the area of cancer diagnosis and treatment research. Finally, the current difficulties and prospects for targeting organelle CDs are prospected.

U-Net convolutional neural network-based modification method for precise fabrication of three-dimensional microstructures using laser direct writing lithography.

In this paper, a modification method based on a U-Net convolutional neural network is proposed for the precise fabrication of three-dimensional microstructures using laser direct writing lithography (LDWL). In order to build the correspondence between the exposure intensity distribution data imported to the laser direct writing system and the surface profile data of the actual fabricated microstructure, these two kinds of data are used as training tensors of the U-Net convolutional neural network, which is proved to be capable of generating their accurate mapping relations. By employing such mapping relations to modify the initial designed exposure intensity data of the parabolic and saddle concave micro-lens with an aperture of 24µm×24µm, it is demonstrated that their fabrication precision, characterized by the mean squared error (MSE) and the peak signal-to-noise ratio (PSNR) between the fabricated and the designed microstructure, can be improved significantly. Specifically, the MSE of the parabolic and saddle concave micro-lens decreased from 100 to 17 and 151 to 50, respectively, and the PSNR increased from 22dB to 29dB and 20dB to 25dB, respectively. Furthermore, the effect of laser beam shaping using these two kinds of micro-lens has also been improved considerably. This study provides a new solution for the fabrication of high-precision three-dimensional microstructures by LDWL.

Enhanced-fluorescent imaging and targeted therapy of liver cancer using highly luminescent carbon dots-conjugated foliate.

Carbon dots (CDs) have shown great potential in drug delivery and biological imaging applications. In this work, a doxorubicin (DOX) delivery carrier and imaging probe for liver cancer-targeted therapy was designed based on CDs with high fluorescence quantum yield (97%), aiming to enhance the antitumor activity and imaging efficiency. Folic acid (FA), which showed high expression in hepatoma cells, was used as targeting components to modify CDs (FA-CDs), and then FA-CDs-DOX was obtained by loading DOX. Results show that CDs and FA-CDs have good biocompatibility, and the DOX release from FA-CDs-DOX is targeted and selective. Confocal microscope demonstrates that FA-CDs-DOX has excellent ability of fluorescence imaging in liver cancer cells. The imaging in vivo shows the fluorescence intensity of FA-CDs-DOX is strong enough to penetrate tumor tissue and skin, further verifying its enhanced-fluorescent imaging effects. Tumor inhibition in vivo indicates that the targeting ability of FA-CDs-DOX is significantly higher than that of free DOX, showing obvious better therapeutic effect. To sum up, the targeted and fluorescent drug delivery system based on CDs with high fluorescence quantum yield show an excellent imaging in vivo and tumor inhibition effect, which provide a novel strategy for promoting the potential clinical application of CDs in liver cancer treatment.

Large-area cavity-enhanced 3D chiral metamaterials based on the angle-dependent deposition technique.

Large-area and high-performance chiral metamaterials are highly desired for practical applications, such as controlling the polarization state of an electromagnetic wave and enhancing the sensor sensitivity of chiral molecules. In this work, cavity-enhanced chiral metamaterials (CECMs) with a large area (1 cm2) have been fabricated by the convenient angle-dependent material deposition technique. The optimal chiral signal (g factor) resonance in the visible waveband can reach about 0.94 with a figure of merit (FOM) of about 5.2, which is about ten times larger than that of chiral metamaterials (CMs) without a cavity (i.e., a g factor of 0.094 with the FOM of about 1.12). Both the theoretical and experimental results demonstrate that the circular conversion components from the anisotropic geometry of CMs play a crucial role in the final chiroptical effect of CECM, which together with the cavity effect enhance both the chiroptical resonance intensity and FOM. Choosing the appropriate deposition parameters can effectively modify the geometric anisotropy of CM and thus the chiroptical effect of CECM. The geometric nanoscale morphology, electromagnetic properties and sensor performance were investigated carefully in this work. The fabricated CECM working in the visible waveband together with the cavity-enhanced scheme provides a competitive candidate for enhancing the performance and the practical applications of CMs.

Measurement of hysteresis loop based on weak measurement.

In this Letter, we propose a technique for hysteresis loop measurement based on weak measurement. By using the photonic spin Hall effect (PSHE) as a probe and combining the quantum weak measurement, the technique's noise can be suppressed greatly. A theoretical model to describe the numerical relation between the amplified shift and Kerr rotation angle is established. Through detecting the amplified shift of the PSHE based on weak measurement, we experimentally measure the hysteresis loops of Ni-Fe alloy film, iron-phthalocyanine (FePc) monolayer film, and Co/FePc double-layer film. The results show that the precision can reach about $ \sim {10^{ - 6}} \;{\rm rad} $∼10-6rad under ordinary experimental conditions, which may have an important application prospect in magneto-optic parameters measurement.

Folic acid-conjugated magnetic ordered mesoporous carbon nanospheres for doxorubicin targeting delivery.

Folic acid-conjugated magnetic ordered mesoporous carbon nanospheres (FA-MOMCNs) are developed as a targeting delivery vehicle of doxorubicin (DOX) in this work. Investigations on DOX loading mechanism show that the loading capacity of FA-MOMCNs is up to 577.12 mg g-1 by means of both physical porous adsorption and covalent interactions, and the pH-dependent drug release is achieved. Excellent biocompatibility of FA-MOMCNs with blood and cells is confirmed by hemolysis and cytotoxicity assays. With the assistance of effective passive and active targeting, DOX-loading FA-MOMCNs can be readily internalized into cancer cell, where the carried DOX can be efficiently released in the acidic microenvironment of the cancer cell for its proliferation inhibition. This controlled release and targeting vehicle of DOX makes it possible to reduce the toxic effect to normal tissues during circulation in the body and is promising for highly efficient chemotherapy.

Quantification and coupling of the electromagnetic and chemical contributions in surface-enhanced Raman scattering.

In surface-enhanced Raman scattering (SERS), both chemical (CE) and electromagnetic (EM) field effects contribute to its overall enhancement. However, neither the quantification of their relative contributions nor the substrate dependence of the chemical effect have been well established. Moreover, there is to date no understanding of a possible coupling between both effects. Here we demonstrate how systematically engineered silver and gold planar and nanostructured substrates, covering a wide range of field enhancements, provide a way to determine relative contributions of chemical and electromagnetic field-enhancement in SERS measurements of benzenethiol. We find a chemical enhancement of 2 to 14 for different vibrational resonances when referencing against a vibrational mode that undergoes minimal CE. The values are independent of substrate type and independent of the enhancement of the electromagnetic intensity in the range from 1 to 106. This absence of correlation between chemical and electromagnetic enhancement resolves several long-standing controversies on substrate and intensity dependence of the chemical enhancement and allows for a more systematic design of SERS substrates with desired properties.

Active perfect absorber based on planar anisotropic chiral metamaterials.

Active chiral plasmonics have attracted a considerable amount of research interest for their power to switch the handedness of chiral metamaterials and the potential applications in highly integrated polarization sensitive devices, stereo display fields, and so on. In this work, we propose a kind of active chiral metamaterial absorber (ACMA) composed by planar anisotropic chiral metamaterials (PACMs) and a metal layer. Our in-depth theoretical analysis indicates that the circular conversion dichroism (CCD) from PACMs plays a crucial role to achieve the active chiroptical effect. The CCD effect can enable a differentiated microcavity-interference effect between the left and right circular incident lights and results in a chiroptical effect related to the equivalent optical length between the PACMs and the metal layer. In simulations, a high-performance ACMA, which are composed by the 'Z'-shaped PACMs, is designed, and the maximum reflection CDR from ACMA can reach 0.882. Meanwhile, the minimum reflection CDR can reach to 0, resulting a very large adjustable range of from 0 to 0.882. The maximum modulation sensitivity, which is defined as Mn=∂CDR/∂n and Md=∂CDR/∂d, can reach to about 1368.252 for d=100um and 0.06157 nm-1 for n=4.5,respectively. In addition to the active chiroptical effect, the designed ACMA also shows excellent performance as a sensor, such as when it is being used as a highly-sensitive temperature sensor. In that case, the minimum detected precision can reach approximately 3.067 * 10-8 °C, if VO2 is used to fill the FP cavity.

Label-free identification of trace microcystin-LR with surface-enhanced Raman scattering spectra.

The analysis of trace microcystin-LR (MC-LR) plays important roles in environmental fields, especially in monitoring domestic water quality and safety, since it has particularly harmful effect on wild and domestic animals as well as humans at low doses. Herein, we combine confocal Raman spectroscopy with SERS-AG substrate to characterize the "fingerprint" information of MC-LR directly. High sensitivity of SERS-AG substrates was verified by utilizing the probe molecule Rhodamine 6 G. Mapping spectra demonstrated good reproducibility of MC-LR identification with label-free surface-enhanced Raman scattering (SERS) strategy. Differences between SERS spectra of MC-LR and R6G, microcystin-RR were evaluated by calculating their scores and loading weights with an unsupervised exploratory principal component analysis method. Then, relationship between Raman intensities and concentrations was preliminary analyzed with SERS spectra of MC-LR and the lowest concentration of MC-LR identification was 10-6 mg L-1 while using SERS-AG substrate. Thereafter, 68.6% quantitative recovery of 10-3 mg L-1 MC-LR in tap water samples was obtained by the proposed label-free SERS method. These results showed that confocal Raman spectroscopy with label-free surface-enhanced Raman scattering strategy can handle the identification of trace MC-LR for monitoring water quality and safety worldwide in future.

Unveiling the spin Hall effect of light in Imbert-Fedorov shift at the Brewster angle with weak measurements.

The Imbert-Fedorov (IF) shift is defined as the transverse shift of barycenter of the entire beam when a circular or elliptically polarized incident beam is reflected. In this work, we examine the IF shift of Gaussian beam at the Brewster angle. Interestingly, the spin Hall effect of light takes place in the IF shift at the same time. Furthermore, this interesting phenomenon is experimentally observed using weak measurements. These findings may have useful applications in spin optics.

Antitumor effects of carbon nanotube-drug complex against human breast cancer cells.

To improve the bio-solubility and sustained-release properties of a carbon nanotube (CNT)-drug complex, the present study used a hydrophilic polymer, polyethylene glycol (PEG), and ß-estradiol (E2), which targets the estrogen receptor in human breast cancer cells (HBCCs), to modify CNTs carrying lobaplatin (LBP) to form E2-PEG-CNT-LBP. The in vitro inhibitory effects against HBCCs and the in vivo pharmacological effect of the complex on heart, liver and kidney tissues were also evaluated. The results indicated that the inhibitory effects of this complex against HBCCs reached 80.44% within 72 h. A blood biochemical test of normal mice indicated that this complex reduced platelet counts, while aspartate aminotransferase levels were increased compared with those in the control group. Histopathological analysis revealed no obvious adverse effects on the heart, liver and kidneys. The in vivo results indicated that the novel E2-PEG-CNT-LBP complex had no obvious toxic effects while exhibiting sustained-release properties. The clearance of E2-PEG-CNT-LBP by non-specific uptake systems was delayed and its clearance was increased compared with LBP alone.

Assessment of physiological responses and growth phases of different microalgae under environmental changes by Raman spectroscopy with chemometrics.

The assessment for cell physiology and growth phases of microalgae plays important roles in ecological and environmental fields since it can be used to forecast water eutrophication level worldwidely. Herein, growth phases and environmental conditions of microalgae were assessed by combining resonance Raman mapping spectroscopy with multivariate analysis methods. And, primary Raman characteristic peaks of microalgae were mined with two-dimensional synchronous spectra. Thereafter, algal growth phases and environmental conditions of microalgae were preliminary classified with different tendencies of characteristic Raman peaks by unsupervised principal component analysis (PCA) and support vector machine (SVM) methods. Our results demonstrated that resonance Raman mapping spectroscopy with PCA and SVM classification models can be used to assess algal growth phases and preliminary predict environmental conditions with characteristic Raman spectra of microalgae in water bodies.

Binary wavefront optimization using a simulated annealing algorithm.

We propose an idea using a simulated annealing algorithm for amplitude modulation to focus light through disordered media. Using 4096 independently controlled segments of an incident wavefront, the intensity of the target signal is enhanced 73 times over the original intensity of the same output channel. The simulated annealing algorithm and existing amplitude control algorithms for focusing through scattering media are compared experimentally. It is found that the simulated annealing algorithm achieves the highest enhancement when the number of iterations required for optimization is the same.

Thermo-sensitively and magnetically ordered mesoporous carbon nanospheres for targeted controlled drug release and hyperthermia application.

A multifunctional nanoplatform based on thermo-sensitively and magnetically ordered mesoporous carbon nanospheres (TMOMCNs) is developed for effective targeted controlled release of doxorubicin hydrochloride (DOX) and hyperthermia in this work. The morphology, specific surface area, porosity, thermo-stability, thermo-sensitivity, as well as magnetism properties of TMOMCNs were verified by high resolution transmission electron microscopy, field emission scanning electron microscopy, thermo-gravimetric analysis, X-ray diffraction, Brunauer-Emmeltt-Teller surface area analysis, dynamic light scattering and vibrating sample magnetometry measurement. The results indicate that TMOMCNs have an average diameter of ~146nm with a lower critical solution temperature at around 39.5°C. They are superparamagnetic with a magnetization of 10.15emu/g at 20kOe. They generate heat when inductive magnetic field is applied to them and have a normalized specific absorption rate of 30.23W/g at 230kHz and 290Oe, showing good potential for hyperthermia. The DOX loading and release results illustrate that the loading capacity is 135.10mg/g and release performance could be regulated by changing pH and temperature. The good targeting, DOX loading and release and hyperthermia properties of TMOMCNs offer new probabilities for high effectiveness and low toxicity of cancer chemotherapy.