Silver@Prussian Blue Core-Satellite Nanostructures as Multimetal Ions Switch for Potent Zero-Background SERS Bioimaging-Guided Chronic Wound Healing.

Metal-organic framework-based metal ion therapy has attracted increasing attention to promote the cascade wound-healing process. However, multimetal ion synergistic administration and accurately controlled ion release are still the challenges. Herein, an aptamer-functionalized silver@cupriferous Prussian blue (ACPA) is established as a metal-based theranostic nanoagent for a chronic nonhealing diabetic wound treatment. Prussian blue offers a programmable nanoplatform to formulate metal ion prescriptions, achieving cooperative wound healing. Silver, copper, and iron ions are released from ACPA controlled by the near-infrared-triggered mild hyperthermia and then synergistically participate in antipathogen, cell migration, and revascularization. ACPA also demonstrates a unique core-satellite nanostructure which enables it with improved surface-enhanced Raman scattering (SERS) capability as potent bacteria-targeted Raman-silent nanoprobe to monitor the residual bacteria during wound healing with nearly zero background. The theranostic feature of ACPA allows high-performance SERS imaging-guided chronic wound healing in infectious diabetic skin and keratitis.

Strong and Ultra-tough Ionic Hydrogel Based on Hyperbranched Macro-Cross-linker: Influence of Topological Structure on Properties.

The application of hydrogels often suffers from their inherent limitation of poor mechanical properties. Here, a carboxyl-functionalized and acryloyl-terminated hyperbranched polycaprolactone (PCL) was synthesized and used as a macro-cross-linker to fabricate a super strong and ultra-tough ionic hydrogel. The terminal acryloyl groups of hyperbranched PCL are chemically incorporated into the network to form covalent cross-links, which contribute to robust networks. Meanwhile, the hydrophobic domains formed by the spontaneous aggregation of PCL chains and coordination bonds between Fe3+ and COO- groups serve as dynamic non-covalent cross-links, which enhance the energy dissipation ability. Especially, the influence of the hyperbranched topological structure of PCL on hydrogel properties has been well investigated, exhibiting superior strengthening and toughening effects compared to the linear one. Moreover, the hyperbranched PCL cross-linker also endowed the ionic hydrogel with higher sensitivity than the linear one when used as a strain sensor. As a result, this well-designed ionic hydrogel possesses high mechanical strength, superior toughness, and well ionic conductivity, exhibiting potential applications in the field of flexible strain sensors.

Microfiber-directed reversible assembly of Au nanoparticles for SERS detection of pollutants.

Surface-enhanced Raman scattering (SERS) spectroscopy has attracted tremendous interest as a highly sensitive label-free tool to detect pollutants in aqueous environments. However, the high cost and poor reusability of conventional SERS substrates restrict their further applications in rapid and reproducible pollutant detection. Here, we report a reliable optical manipulation method to achieve rapid photothermal self-assembly of Au nanoparticles (AuNPs) in water within 30 s by a tapered optical fiber, which is utilized for highly sensitive SERS substrate preparation. The results show that the SERS substrate achieves low detection limits of 10-9 mol/L with an enhancement factor (EF) of 106 for chemical pollutants solutions, including thiram, pyrene, and rhodamine 6G. The SERS enhancement effect based on assembled AuNPs was more than 20 times that based on a gold colloid solution. As a result, the smart reversible assembly of AuNPs exhibits switchable plasmonic coupling for tuning SERS activity, which is promising for the application of SERS-based sensors and environmental pollutant detection.

Mussel-inspired hydrogels for fast fabrication of flexible SERS tape for point-of-care testing of ß-blockers.

The flexible surface-enhanced Raman scattering (SERS) platform has ceaselessly propelled the development of point-of-care testing (POCT) in diverse fields. Herein, we report a facile strategy for the SERS-chemometric analysis of four ß-blockers (bisoprolol, metoprolol, acebutolol and esmolol) based on a super-sticky mussel-inspired hydrogel SERS tape. The surface morphology and mechanical properties of the hydrogel tape can be easily controlled by adjusting the compositional ratio. The optimized tape with excellent toughness and adhesiveness allows efficient collection of analytes through a simple "paste and peel off" approach, further by spraying with silver nanoparticles using a household sprayer to instantly assemble a flexible SERS substrate, the analytes can then detected by a portable Raman spectrometer. This POCT strategy enables the identification and discrimination of four similar ß-blockers with high sensitivity and accuracy in combination with the statistical algorithms. The developed SERS tape is finally utilized for the recognition of ß-blockers in simulated urine solution, which realizes a limit of detection of 1.0 ng mL-1, revealing a promising potential of this SERS-based POCT for the clinical detection of doping abuse.

A Versatile Strategy for Multi-Stimuli-Responsive Fluorescent Material Based on Cross-Linking-Induced Emission: Applications in Encryption.

A versatile strategy for smart fluorescent materials is lacking due to their diverse responding mechanisms and incompatibility of responsive behaviors. Herein an adaptable strategy is presented toward a multi-stimuli-responsive fluorescent material with stage-by-stage responsive behavior by blending linear polymers modified with different stimulus-responsive moieties and AIE cross-linker. Under stimuli, the linear polymer can cross-link with the cross-linker to form networks, which intrinsically restrict the intramolecular rotation of the AIE molecule to induce strong emission. A unified stimuli-responsive mechanism is involved in that various stimuli are transferred through the organized "stimulus-crosslink-emission" process. This strategy ensures the compatibility of different stimuli-responses and the adjustability of stimulus-response behavioral logic. These multi-stimuli-responsive fluorescent materials exhibited strong accessibility and adaptability for information encryption.

Photothermal microfluidic-assisted self-cleaning effect for a highly reusable SERS sensor.

The synergistic integration of optofluidic and surface enhanced Raman scattering (SERS) sensing is a new analytical technique that provides a number of unique characteristics for enhancing the sensing performance and simplifying the design of microsystems. Here, we propose a reusable optofluidic SERS sensor by integrating Au nanoisland substrate (AuNIS)-coated fiber into a microfluidic chip. Through both systematic experimental and theoretical analysis, the sensor enables efficient self-cleaning based on its optical-to-heat-hydrodynamic energy conversion property. Besides, the sensor exhibits the instrument detection limit down to 10-13mol/L and enhancement factor of 106 for Rhodamine 6G. Our optofluidic SERS sensor with such a photothermal microfluidic-assisted self-cleaning method has the advantages of portability, simple operation, and high cleaning efficiency, which will provide a new, to the best of our knowledge, concept and approach for cost-effective and reusable sensors.

Vortices-interaction-induced microstreaming for the pump-free separation of particles.

Microfluidic techniques have emerged as promising strategies for a wide variety of synthetic or biological sorting. Unfortunately, there is still a lack of sorting with automatic and handy operation. In contrast to passively generated vortices, the thermocapillary vortices produced by temperature gradient have the advantages of flexible manipulation, stable strength, and simple integration. In this Letter, we present a device used for the pump-free separation of particles through vortices interaction without external fluidic control systems required for the majority of existing devices. Specifically, the device induces a different flow type upon the actuation of optical power, and the flow functions, such as simultaneous pumping and sorting, agree with stimulation results very well. More importantly, our developed sorting device can achieve separations by means of tunable cutoff diameter size. Therefore, this versatile device can be utilized to sort complex samples with the advantages of portability, user-friendly control, and automation.

Generation and manipulation of oil-in-water micro-droplets by confined thermocapillary microvortices.

Optofluidic manipulation of droplets is critical in droplet-based microfluidic systems for chemistry, biology, and medicine. Here, we reported a thermocapillary microvortices-based manipulation platform for controlling oil-in-water droplets through integrating a photothermal waveguide into a microfluidic chip. The sizes and shapes of the droplets can be controlled by adjusting optical power or positions of the water-oil interface. Here, teardrop-shaped droplets, which can encapsulate and accumulate mesoscopic matters easily, were generated when the water-oil interface and the channel boundaries approached the photothermal waveguide center simultaneously. The results showed that the thermocapillary microvortices have good controllability of droplet positions, droplet volumes, and encapsulated-particle distribution and thus it will be a powerful droplet manipulation strategy for microreactors and microcapsules.

Investigating the autophagy pathway in silver@gold core-shell nanoparticles-treated cells using surface-enhanced Raman scattering.

Previous studies have shown that nanoparticles can induce autophagy, and the main approach for investigating autophagy induced by nanoparticles is via traditional methods such as TEM and biochemical assay. These methods measurements suffer from the disadvantages of complicated experimental processes, cell destruction, as well as lack of characterization of individual stages of the autophagy pathway. Surface-enhanced Raman scattering (SERS) has been extensively used in biological applications. With the combination of SERS and chemometric methods, such as principal component analysis-linear discriminant analysis (PCA-LDA), identification and distribution mapping of endosomes and lysosomes in the endocytosis of Au nanoparticles has been achieved by segregating the spectra from complex SERS data sets in the previous study. In this study, silver@gold core-shell nanoparticles (Ag@Au NPs) were synthesized by reduction of gold ions on the surface of the silver nanoparticles, and the autophagy induced by Ag@Au NPs was studied with Ag@Au NPs serving both as an autophagy inducer and as a high-performance SERS substrate. Pro-survival autophagy induced by Ag@Au NPs was proved by the western blot assay, flow cytometry and fluorescent staining. Furthermore, the autophagy pathway in Ag@Au NPs-treated cells was first elucidated by SERS combined with a modified reference-based PCA-LDA methodology. This study provides a feasible way of using SERS to elucidate the autophagy pathway induced by nanoparticles.

[Polypyrrole Functionalized Gold Nanorods as Novel Contrast Agents for Optical Coherence Tomography].

Polypyrrole (PPy) is easy-prepared with good biocompatibility and strong absorption in near-infrared (NIR) region which can serve as both the photothermal therapeutic agent and contrast agent of optical coherence tomography (OCT) imaging. Herein, gold nanorod (GNR) modified with PPy (GNR-PPy) as contrast agent for optical coherence tomography imaging was investigated. GNR-PPy was synthesized via one-pot facile oxidative polymerization by using pyrrole and GNR as starting materials. Nanoparticles were characterized using ultraviolet-visible absorbance spectroscopy, Raman spectroscopy and transmission electron microscopy. A xenograft tumor mouse model was fabricated to study the OCT contrast effect of GNR-PPy on breast tumor. An OCT system equipped with an 840 nm SLED was used for OCT imaging of the tumors injected with gold nanostructures. The experimental results indicated that the penetration depth of the OCT signals from tumors injected with GNR-PPy was lower than that from tumors injected with gold nanorods, which could be ascribed to the stronger light activity of GNR-PPy in NIR region. To quantitatively analyze the contrast effect, the attenuation coefficients were extracted from the OCT images of tumors injected with the nanostructures. In comparison with the attenuation coefficient extracted from the OCT images containing GNR, the attenuation coefficient of tumors injected with GNR-PPy was significant higher. It was concluded that gold nanorods modified with polypyrrole can enhance the light absorption in near-infrared much better, which would provide a possible detection means for enhancing the contrast effect of tumor tissues.

Food-borne bacteria analysis using a diatomite bioinspired SERS platform.

Rapid and sensitive detection of food-borne bacteria has remained challenging over the past few decades. We propose a surface-enhanced Raman scattering sensing strategy based on a novel bioinspired surface-enhanced Raman scattering substrate, which can directly detect dye molecular residues and food-borne pathogen microorganisms in the environment. The surface-enhanced Raman scattering platform consists of a natural diatomite microporous array decorated with a metal-phenolic network that enables the in situ reduction of gold nanoparticles. The as-prepared nanocomposites display excellent surface-enhanced Raman scattering activity with the lowest limit of detection and the maximum Raman enhancement factor of dye molecules up to 10-11 M and 1.18 × 107, respectively. For food-borne bacterial detection, a diatomite microporous array decorated with a metal polyphenol network and gold nanoparticle-based surface-enhanced Raman scattering analysis is capable of distinguishing the biochemical fingerprint information of Staphylococcus aureus and Escherichia coli, indicating the great potential for strain identification.

Graphene oxide based surface-enhanced Raman scattering probes for cancer cell imaging.

The intrinsic Raman signals provide the potential of graphene oxide (GO) for cellular imaging. Herein, novel surface-enhanced Raman scattering (SERS) labels based on GO-Ag nanoparticle (NP) composites are developed for fast cellular probing and imaging. The optimum SERS signals of the hybrids can be well controlled by adjusting the weight ratio between AgNO(3) and GO. Utilizing GO-AgNPs as the highly sensitive optical probes, fast SERS imaging of cancer cells is realized with a very short integration time of about 0.06 s per pixel. Furthermore, folic acid (FA) is covalently conjugated to GO for targeting specific cancer cells with folate receptors (FRs). Targeted SERS images can be acquired after 2 h incubation with FA-GO-AgNPs, which are specifically located on the surface of FR-positive cancer cells. In conclusion, the GO-based Raman probes mentioned here open up exciting opportunities for biomedical imaging.

[Green synthesis of silver nanoparticles and their application in SERS].

In the present paper, we have successfully synthesized silver nancomparticles by reducing of silver nitrate in alkaline solution via 60 degrees C water bath for 20 minutes with the use of tyrosine, a nontoxic and green macromolecule, as a reducing and stabilizing agent. The formation of silver nanoparticles was observed visually by color change of the solutions (from faint yellow to brown yellow). The morphologies of the Ag NPs were characterized by UV-Vis absorption spectroscopy and transmission electron microscopy (TEM). The UV-Vis absorption peak of silver nanoparticles located at 412 nm. The TEM image of silver nanoparticles indicated that the diameters of nanospheres are mainly in the range 15-25 nm. In order to evaluate the SERS activity of the silver nancomparticles, crystal violet and folic acid were used as the Raman probe molecule. The experimental results indicated that there are two ascendancies, firstly, the approach is convenient and the reaction condition is facile, secondly, tyrosine is a water-soluble, nontoxic and biodegradable macromolecule, which makes this approach provide a green strategy to prepare Ag NPs. Significantly, the synthesized Ag NPs exhibits good surface enhanced Raman scattering (SERS) activity as SERS substrates to detect crystal violet and folic acid in aqueous solution.

A UV-induced self-reinforced hydrogel based on in situ hydrophobic aggregation of strained 1,2-dithiolane rings.

A novel responsive hydrogel exhibiting self-reinforcement and self-healing capacity was developed based on the hydrophobic aggregation of strained 1,2-dithiolane rings. Oligomerization of 1,2-dithiolane within hydrophobic domains under UV irradiation not only reinforced the hydrogel but also maintained its dynamic cross-linked nature by converting the intraring dynamic S-S bond to an outer one.

Label-Free Surface-Enhanced Raman Scattering Bioanalysis Based on Au@Carbon Dot Nanoprobes.

Surface-enhanced Raman scattering (SERS) technology has attracted more and more attention in the biomedical field due to its ability to provide molecular fingerprint information of biological samples, as well as its potential in single-cell analysis. This work aims to establish a simple strategy for label-free SERS bioanalysis based on Au@carbon dot nanoprobes (Au@CDs). Here, polyphenol-derived CDs are utilized as the reductant to rapidly synthesize core-shell Au@CD nanostructures, which allows powerful SERS performance even when the concentration of methylene blue (MB) is as low as 10-9 M, due to the cooperative Raman enhancement mechanism. For bioanalysis, Au@CDs can serve as a unique SERS nanosensor to identify the cellular components of biosamples (e.g., cancer cells and bacteria). The molecular fingerprints from different species can be further distinguished after combination with the principal component analysis. In addition, Au@CDs also enable label-free SERS imaging to analyze intracellular composition profiles. This strategy offers a feasible, label-free SERS bioanalysis, opening up a new prospect for nanodiagnosis.

A novel alternative strategy for monitoring and insight into liver fibrosis progression: The combination of surface-enhanced Raman spectroscopy (SERS) and gut microbiota.

Nowadays, the studies on the interaction and relationship between the intestinal microorganisms and liver diseases are increasing. However, it is still a huge challenge for the in-depth investigation and dynamic monitoring of such a complex network. Herein, a significant discovery was made. A strong association between gut microbial structural and functional genomics and SERS spectra of hepatocytes were revealed. Based on the study of gut microbes and SERS spectra, complementary information could be provided for the mechanism analysis of related diseases. Liver fibrosis, a chronic liver disease that lack specific cure was thus comprehensive studied. Liver targeting gold nanoparticle dimers were prepared as the SERS tags, and abundant SERS peak signals were acquired. Meanwhile, the gut microbiomes were also comparative studied. The changes of carbohydrates and lipids in liver cells were observed at the early stages of liver fibrosis, and TLR4 (toll-like receptors 4) was activated to elicit immune responses. Then again, oxidative stress, endotoxin and serum inflammatory factors were the major observations at the late stages. The SERS signals and the microbiome analysis were well confirmed and complemented each other, which suggested that the detection strategy could be another valuable method for the "gut-liver axis" study.

[Raman spectroscopic study on the influence of ultraviolet-A radiation on collagen I].

Raman spectroscopy was used to study the influence of ultraviolet-A(UV-A) radiation on collagen I. The Raman spectra of collagen I and that after 90 min UV-A radiation were reported. The results proved that irradiation with 90 min UV-A caused the change in the structures of collagen I. Intramolecular hydrogen bonds were broken, and the hydrogen bonding system was changed. The intensity of helix was decreased, while the intensity of the disordered conformation in proteins such as random coil was increased. Otherwise, the UV-A radiation influenced the hydroxylation of proline and the content of hydroxyproline was reduced. The changes caused by UV-A radiation could damage the triple helical structure of collagen I. It would lead to a series of changes, such as the destruction of collagen fibers during the photoaging of skin.

[In vivo reflectance spectroscopy study of different clearing agents on human skin optical clearing].

The changes of skin tissue reflectance spectroscopy before and after being treated with the optical clearing agents of three different types of optical clearing within the wavelength rang of 400-1 000 nm, and the degree of changes in reflectance spectroscopy of each group skin during 0-60 min at 580 nm in vivo were real-time dynamically researched. The reflectance spectroscopy of skin tissue before and after being dealt by the optical clearing agents of glycerol, glucose and propylene glycol was measured using a USB-4000 fiber spectrophotometer at 0, 10, 20, 30, 40, 50 and 60 min. The results showed that the reflectance spectral intensity was distinctly decreased, but the reflectance was significantly increased gradually with the time prolonged. However, different optical clearing agents have different clearing progress. The relative decrease of reflectance of palm skin tissue before and after being dealt by the optical agents of 40% glycerol, 40% glucose and 40% propylene glycol during 10, 20, 30, 40, 50 and 60 min at the wavelength 580 nm is 5%, 7%, 9%, 10%, 11% and 12%, 9%, 13%, 16%, 19%, 21% and 22%, and 14%, 22%, 29%, 32%, 34% and 35%, respectively. The significant improvement in light transmittance and enhancement of light penetration through tissue was demonstrated for all solutions. The effect and processes of optical clearing of skin tissue is not only closely related to the choosing of the clearing agent type, but also related to the treatment time with the skin tissue. The clearing progress of different type optical clearing agent showed the order of 40% propylene glycol, 40% glucose and 40% glycerol.

SERS diagnosis of liver fibrosis in the early stage based on gold nanostar liver targeting tags.

In order to realize the accurate and early diagnosis of liver fibrosis, a long slow pathological process which may lead to cirrhosis or even liver cancer, liver targeting tags made up of gold nanostars and glycyrrhetinic acid are reported in this paper. Gold nanostars (GNSs) and GNS liver targeting tags (GLTTs) were injected into model mice with stage S1 liver fibrosis and normal mice via the tail vein respectively, then the SERS spectra were collected. GLTTs had a better detection effect on liver tissue than unmodified GNSs (12.85 times), and better detection reproducibility as well. Moreover, according to the MTT and survival analysis experiments, GLTTs also had better biocompatibility. Hence, the changes of 10 SERS signals and other substances in the early stage of liver fibrosis were analyzed at the molecular level, and the SERS characteristic peaks that could be used for the diagnosis of early liver fibrosis were screened out. Revealed by the experimental results, the GLTTs designed and prepared were applicable to the efficient SERS detection of early liver fibrosis in mice, and the strategy we have proposed might be a potential approach for the early diagnosis of this disease in clinics.

Photo-induced synthesis of molybdenum oxide quantum dots for surface-enhanced Raman scattering and photothermal therapy.

By means of a simple and photo-induced method, four colors of molybdenum oxide quantum dots (MoOx QDs) have been synthesized, using Mo(CO)6 as the structural guiding agent and molybdenum source. The as-prepared MoOx QDs display diverse optical properties due to the different configurations of oxygen vacancies in various nanostructures. Among them, crystalline molybdenum dioxide (MoO2) with a deep blue color shows the most intense localized surface plasmon resonance effect in the near-infrared (NIR) region. The strong NIR absorption endows MoO2 QDs with a high photothermal conversion efficiency of 66.3%, enabling broad prospects as a photo-responsive nanoagent for photothermal therapy of cancer. Moreover, MoO2 QDs can also serve as a novel semiconductor substrate for ultrasensitive surface-enhanced Raman scattering (SERS) analysis of aromatic molecules, amino acids and antibiotics, with SERS performance comparable to that of noble metal-based substrates. The therapeutic applications of MoO2 QDs open up a new avenue for tumor nanomedicine.