New features of edge-selectively hydroxylated graphene nanosheets as NIR-II photothermal agent and sonothermal agent for tumor therapy.

Second near-infrared (NIR-II) laser-mediated photothermal therapy and sonothermal therapy using low-intensity focused ultrasound exposure for tumors have attracted increasing attention owing to their ability to penetrate deep tissues and provide noninvasive ablation with high therapeutic efficacy. However, their applications were limited by the shortness of optimal NIR-II photothermal agents and sonothermal agents. In this study, we discovered that the edge-selectively hydroxylated graphene nanosheets (EHG NSs) with excellent water dispersibility and an "intact conjugated plane" were not only an outstanding NIR-II photothermal agent but also an effective sonothermal agent for tumor therapy. EHG NSs were incorporated into an injectable adhesive thermosensitive hydrogel with a characteristic sol-gel phase transition behavior. EHG NSs endowed the injectable hydrogel with an exceptional photothermal effect under the laser irradiation (1064 nm, 1.0 W cm-2) as well as an effective sonothermal effect under ultrasonic exposure (3.0 MHz, 2.1 W cm-2), effectively killing tumor cells in vitro and inhibiting tumor growth after intratumoral injection. Especially, the NIR-II photothermal therapy based on the hybrid hydrogel completely ablated the primary tumors and effectively activated systemic anti-tumor immune responses benefiting from the protein adsorption capacity of the injectable hydrogel, significantly inhibiting the growth of the distal tumors. Collectively, EHG nanosheets loaded in the injectable hydrogel will be a promising "all-rounder" for noninvasive deep penetrating thermotherapy and a potent platform that integrates various therapies.

Ultrasmall Metal TPZ Complexes with Deep Tumor Penetration for Enhancing Radiofrequency Ablation Therapy and Inducing Antitumor Immune Responses.

Radiofrequency ablation (RFA) is one of the most common minimally invasive techniques for the treatment of solid tumors, but residual malignant tissues or small satellite lesions after insufficient RFA (iRFA) are difficult to remove, often leading to metastasis and recurrence. Here, Fe-TPZ nanoparticles are designed by metal ion and (TPZ) ligand complexation for synergistic enhancement of RFA residual tumor therapy. Fe-TPZ nanoparticles are cleaved in the acidic microenvironment of the tumor to generate Fe2+ and TPZ. TPZ, an anoxia-dependent drug, is activated in residual tumors and generates free radicals to cause tumor cell death. Elevated Fe2+ undergoes a redox reaction with glutathione (GSH), inducing a strong Fenton effect and promoting the production of the highly toxic hydroxyl radical (•OH). In addition, the ROS/GSH imbalance induced by this treatment promotes immunogenic cell death (ICD), which triggers the release of damage-associated molecular patterns, macrophage polarization, and lymphocyte infiltration, thus triggering a systemic antitumor immune response and noteworthy prevention of tumor metastasis. Overall, this integrated treatment program driven by multiple microenvironment-dependent pathways overcomes the limitations of the RFA monotherapy approach and thus improves tumor prognosis. Furthermore, these findings aim to provide new research ideas for regulating the tumor immune microenvironment.

Killing Two Birds with One Stone: Shape-Memory Cryogels for Hemostasis and Wound Repair.

The development of shape-memory hemostatic agents is crucial for the treatment of deep incompressible bleeding tissue. However, there are few reports on biomaterials that can monitor bacterial infection at the wound site in real time following hemostasis and effectively promote repair. In this study, we propose a multifunctional QCSG/FLZ cryogel composed of glycidyl methacrylate-functionalized quaternary chitosan (QCSG), fluorescein isothiocyanate (FITC), and a lysozyme (LYZ)-modified zeolitic imidazolate framework (ZIF-8) for incompressible bleeding tissue hemostasis and wound repair. QCSG/FLZ cryogels possess interconnected microporous structure and enhanced mechanical properties, allowing them to be molded into different shapes for effective hemostasis in deep incompressible wounds. Furthermore, the fluorescence quench signal of QCSG/FLZ cryogels enables timely monitoring of bacterial infection when wound triggers infection. Meanwhile, the acidic microenvironment of bacterial infection induces structural lysis of ZIF-8, releasing LYZ and Zn2+, which effectively kill bacteria and accelerate wound repair. In conclusion, our study not only provides potential application of QCSG/FLZ cryogels for hemostasis in deep incompressible wounds but promisingly promotes the development of a tissue repair technique.

Self-assembled emulsion gel based on modified chitosan and gelatin: Anti-inflammatory and improving cellular uptake of lipid-soluble actives.

To obtain a green carrier for intestinal targeted delivery, an emulsion gel was designed by the self-assembly between gelatin and Pickering emulsion based on gallic acid modified-chitosan nanoparticles (GCS NPs). The emulsion gels loaded with garlic essential oil (Geo) and curcumin (Cur) were abbreviated as GOEG and GCEG, respectively. Meanwhile, the sodium alginate bead loaded with Geo (GOEGS3) and the bead loaded with Cur (GCEGS) were prepared as controls. Results demonstrated that the emulsion gels significantly improved the bioaccessibility of Geo and Cur, showing great intestinal targeting delivery properties comparable to that of sodium alginate beads. Moreover, Caco-2 cell experiments indicated that GOEG and GCEG displayed good biocompatibility and enhanced cellular uptake of Geo and Cur. The emulsion gels also exhibited excellent anti-inflammatory properties in the lipopolysaccharide-induced cell model, exhibiting great potential for clinical application. This work provides some references for the preparation of multifunctional emulsion gels with excellent delivery performance by a green method.

Sodium caseinate decorating on shellac nanoparticles as a stabilizer for the encapsulation of quercetin.

To protect quercetin and address some of the barriers about shellac as a delivery carrier, we investigated the effects of sodium caseinate surface decoration on the formation, stability, and physiochemical properties of shellac nanoparticles (SNPs) for the first time. Herein, 0.3% caseinate was selected to prepare the quercetin-loaded shellac/sodium caseinate complex nanoparticles (SQCNPs), ensuring stable formation of nanoparticles and preventing irreversible aggregation of SNPs in acid. Fourier transform infrared spectroscopy and complex nanoparticle dissociation test indicated SQCNPs were fabricated based hydrophobic and hydrogen-bonding interactions among Que, shellac, and caseinate. Besides, the modification of sodium caseinate can address salt instability and low redispersibility and improve encapsulation efficiency of SNPs. Meanwhile, SQCNPs possessed good antioxidant capacity, low cytotoxicity and controlled release in simulated gastrointestinal digestion. In summary, this work might open up a new, green, and sustainable method to design a bioactive substance delivery system by employing shellac as a vehicle.

Amphiphilic nano-delivery system based on modified-chitosan and ovalbumin: Delivery and stability in simulated digestion.

Nano-delivery systems play an important role in the development of nutritional supplements due to their efficient encapsulation and delivery properties for nutrients. Herein, we prepared protein-polysaccharide nanoparticles as a novel amphiphilic nano-delivery system based on gallic acid modified chitosan (GCS) and ovalbumin (OVA) by pH-driven and calcium ion crosslinking. The nanoparticles loaded with hydrophilic riboflavin (Rib) and hydrophobic quercetin (Que) as nutrient models were abbreviated as GCS-OVA-Rib NPs and GCS-OVA-Que NPs, respectively. Their encapsulation efficiencies for Rib and Que. were 66.36 % and 96.61 %, respectively. In addition, GCS-OVA-Rib NPs and GCS-OVA-Que NPs showed antioxidant activity as well as good stability and delivery capacity for Rib and Que. in simulated digestion with release ratios of 78.38 % and 84.15 %, respectively. More importantly, GCS-OVA-Rib/Que. NPs performed good biocompatibility for further applications. Overall, this work provides some useful insights for the design of novel amphiphilic nano-delivery systems based on polysaccharides and proteins.

NIR-regulated dual-functional silica nanoplatform for infected-wound therapy via synergistic sterilization and anti-oxidation.

Nature-derived bioactive components and photothermal synergistic therapy bring potential strategies for fighting bacterial infection and accelerating would healing by virtue of their excellent therapeutic efficiencies and ignorable side effects, where photothermal property not only acts as sterilization energy but also as a doorkeeper to control the natural component release. Herein, by integrating the excellent antibacterial property of cinnamaldehyde (CA) and the outstanding photothermal performance of copper sulfide nanoparticles (CuS NPs), a multifunctional nanoplatform of SiO2 @CA@CuS nanospheres (NSs) is constructed with silica nanosphere (SiO2 NSs) as carrier. SiO2 @CA@CuS NSs exhibit photothermal property, bacterial absorption capacity, extraordinary antibacterial activity and antioxidant property. Mechanism characteriazation and antibacterial experiment indicate that positive charged SiO2 @CA@CuS can adhere to the negative charged surface of bacteria, and quickly kill bacteria through the synergistic action of the released CA and heat produced under near infrared light (NIR) irradiation at 980 nm. The sterilization efficiencies for Escherichia coli (E. coli) and S. aureus reach 99.86% and 99.84%, respectively. Furthermore, NIR-regulated SiO2 @CA@CuS perform great biocompatibility, as well as effective effects for accelerating S. aureus-infected wound healing at a low photothermal temperature (45 °C) relying on synergistic sterilization and anti-oxidation.

"Lighting-up" methylene blue-embedded zirconium based organic framework triggered by Al3+ for advancing the sensitivity of E. coli O157:H7 analysis in dual-signal lateral flow immunochromatographic assay.

The sensitive detection of foodborne pathogens is of great significance for ensuring food safety and quality. Herein, on the basis of methylene blue-embedded zirconium based organic framework (UIO@MB) as the remarkable capture carrier and signal indicator, with the Al3+-assisted the fluorescent signal response, we developed a label-free and dual-signal lateral flow immunochromatographic assay (LDLFIA) for sensitive detection of Escherichia coli (E. coli) O157:H7. The UIO@MB sensing carrier without monoclonal antibodies (mAbs) was manufactured, which adhered to bacteria to form the UIO@MB-E. coli O157:H7 conjugate, resulting in visible blue band. Then the fluorescent response of the OH-rich UIO@MB was excited by introducing Al3+, arising from capturing of Al3+ by -OH through coordination and electrostatic affinity, thus generating a green fluorescent band. Impressively, a smartphone-based portable reading system was developed that can reflect the test results of UIO@MB-LDLFIA immediately. Under optimum conditions, UIO@MB-LDLFIA can complete colorimetric and fluorescent mode detection within 90 min, with a detection sensitivity of 103 CFU/mL, which were 100 times lower than traditional gold nanoparticles-based LFIA and polymerase chain reaction (PCR). Moreover, the feasibility of the method was further evaluated by the determination of E. coli O157: H7 in drinking water and cabbage with average recoveries of 85.1-123.0%.

A bacteria-triggered wearable colorimetric band-aid for real-time monitoring and treating of wound healing.

Early diagnosis of bacterial infection and tracking of treatment effect are of great importance for developing a "sense-and-treat" integrated system. Herein, we developed a bacteria-triggered, portable, wearable and colorimetric film-based band-aid (FBA) for closed-loop monitoring and light-controlled therapy of wound infection. FBA with high photothermal conversion efficiency of 52.56% was prepared by wrapping Bi2S3 nanoflowers (BS NFs) loaded with rhodium nanoparticles (Rh NPs) and bromothymol blue (BTB) into LB agar film, integrating bacteria-triggered color change, photothermal/photodynamic therapy (PTT/PDT) synergistic bactericidal therapy and agar-based band aid in one intelligent system. Initially, FBA effectively simulates the pH sensing mechanism, and monitors the occurrence of bacterial infections within 5 min through color changes of Staphylococcus aureus (S. aureus) from blue to yellow and Escherichia coli (E. coli) from yellow to blue. Additionally, the short-term and controlled antibacterial strategy of "one light dual-mode responses" (photothermal and photodynamic responses) was implemented with the introduce of near-infrared (NIR). Ultimately, the effectiveness of FBA was fully validated in the monitoring and treating of S. aureus-infected mouse wounds. Notably, the designed FBA decisively abandoned off-target side effects maximizing the treatment effect and nakedly tracking therapeutic situation in real time, contributing an effective antibacterial alternative strategy for reducing the use of antibiotics. To the best of our knowledge, such integrated system is still unreported on film-fixed model. In view of the advantages of the low cost and convenience of the simple device, the integrated design is expected to provide a solution for the development of a closed-loop biomedical system combining diagnosis and treatment.

Fabrication and Characterization of Quercetagetin-Loaded Nanoparticles Based on Shellac and Quaternized Chitosan: Improvement of Encapsulation Efficiency and Acid and Storage Stabilities.

Shellac can be used as an ideal delivery vehicle to deliver and protect the hydrophobic quercetagetin; the barriers such as low acid stability and encapsulation efficiency, however, heavily impede the application of shellac. The purpose of this work is to prepare quercetagetin-loaded shellac-quaternized chitosan nanoparticles (Que-Sh-QCS NPs) to overcome these challenges. Herein, quaternized chitosan, with 14% degree of substitution, was successfully synthesized via a quaternization modification. The concentration of quaternized chitosan over 0.05% can prevent the aggregation of shellac nanoparticles at the acid. The encapsulation efficiency of quercetagetin obviously increased from 37.92 to 65.48% with the concentration of QCS varying from 0 to 0.05%. Meanwhile, Que-Sh-QCS0.05 NPs possessed good storage stability, antioxidant property, biocompatibility, and controlled release. Therefore, quaternized chitosan can improve the encapsulation efficiency and acid and storage stabilities of nutraceutical-loaded shellac nanoparticles, providing a new insight into the application of shellac in cosmetics, pharmaceuticals, and food.

Well-orientation strategy for direct binding of antibodies: Development of the immunochromatographic test using the antigen modified Fe2O3 nanoprobes for sensitive detection of aflatoxin B1.

One of the major concerns in the application of nanocarriers in biosensing is the impair of the recognition molecules bioactivity loaded on their surfaces due to harsh and laborious cross-linking and random orientation, resulting in unsatisfactory sensitivity. Herein, we proposed a novel immunochromatographic test strip (FNS-ag-DICTS) by taking advantage of the antigen (ag) modified Fe2O3 nanostructures (FNSs) as new signal tags and goat anti-mouse IgG labeling on the detection line instead of ag, which was used for sensitive detection of aflatoxin B1 (AFB1). The fabricated FNS-ag can orientate the Fab region of monoclonal antibodies (mAbs), waiving the intrinsic limitations of traditional nanomaterials labeled mAbs. Under optimal conditions, FNS-ag-DICTS possessed excellent specificity and a wide detection range, with a visual limit of detection (vLOD) of 0.0125 ng mL-1. In addition, the biosensor successfully detected AFB1 in peanut, green bean and corn, with an average recovery rate of 82.8-124.9%.

Near-Infrared Light-Regulated Drug-Food Homologous Bioactive Molecules and Photothermal Collaborative Precise Antibacterial Therapy Nanoplatform with Controlled Release Property.

Herein, a collaborative precise antibacterial wound healing therapy nanoplatform integrating drug-food homologous bioactive molecule (cinnamaldehyde, CA) with photothermal therapy (PTT) is presented. Copper-gallic acids-cinnamaldehyde-polydopamine nanorods (Cu-GA-CA-PDA NRs) with near-infrared light (NIR)-controlled CA release property are fabricated, which also integrate CA and photothermal synergistic sterilization, as well as antioxidant, anti-inflammatory, and anti-infection capacities. The characteristics of NIR-mediated CA release and photothermal response of Cu-GA-CA-PDA NRs support their excellent sterilization performance in vitro/in vivo. In addition, under the guidance of NIR, Cu-GA-CA-PDA NRs can hinder the formation of inflammatory cells, reduce oxidative stress damage, accelerate the regeneration of skin tissues in S. aureus-infected wound sites, and achieve the goal of promoting wound healing. Therefore, NIR-mediated Cu-GA-CA-PDA NRs with multifunctional biological activities provide a highly competitive strategy for curing bacteria-infected wounds.

Surface Selenylation Engineering for Construction of a Hierarchical NiSe2/Carbon Nanorod: A High-Performance Nonenzymatic Glucose Sensor.

As glucose (Glu) is an essential substance for metabolism as well as a symbol to diagnose diabetes, the demand of Glu sensors has increased significantly in recent decades. In this work, a hierarchical Ni-based electrochemical enzyme-free Glu sensor, namely, NiSe2/CNR (carbon nanorod), was engineered through a facile thermal treatment using dimethylglyoxime dinickel salt with selenium (Se) powder. The prepared NiSe2/CNR not only subtly introduces a hierarchical structure with rod-like carbon nanorods and rock-like NiSe2 nanoparticles, which are extremely helpful in offering a greater catalytic activity area and more catalytic active sites, but also incorporates the Se element to increase the inherent activity. The fabricated NiSe2/CNR exhibits distinguished performance for Glu detection in alkaline electrolytes with linear ranges of 0.5-411 µM and 411 µM to 6.311 mM, high sensitivities of 3636 µA mM-1 cm-2 at low concentrations, and 2121 µA mM-1 cm-2 at high concentrations, as well as a low detection limit of 380 nM (S/N = 3). It also possesses favorable reproducibility, stability, and long-term storage capacity. The practical feasibility of NiSe2/CNR was also validated by detecting Glu in human serum. Moreover, the prepared hierarchical NiSe2/CNR is of general interest for the construction of hierarchical Ni-based sensors.

Conversional fluorescent kiwi peel phenolic extracts: Sensing of Hg2+ and Cu2+, imaging of HeLa cells and their antioxidant activity.

The valorization, resource generation and the functional characteristic exploration of domestic waste still face enormous challenges. Kiwi peels, a common kind of fruit waste, contain a large amount of phenolic substances, including polyphenols, flavonoids, etc., which can be explored and reused in food and biomedical fields. By ultrasonic assisted extraction technology, we obtained conversional fluorescence kiwi peel phenolic extracts (PE) which possessed gradient magenta fluorescence relying on the content of ethanol in the solution, as well as strong antioxidant activity. Besides, metal ions sensing assay revealed that PE can specifically sense Hg2+ and Cu2+ (LOD: 1.16 and 0.17 µM, respectively) accompanied with a fluorescence conversion from magenta fluorescence to blue. Moreover, employing the prepared PE as fluorescent probes, imaging of HeLa cells can be easily achieved with satisfactory resolution. Additionally, PE was incorporated into the gelatin matrix, successfully fabricating a green, edible degradable film with excellent antioxidant activity.

Multifunctional chitosan-copper-gallic acid based antibacterial nanocomposite wound dressing.

Antibacterial wound dressings can effectively avoid the residual of antibacterial nanomaterials for injection in vivo, reduce their biological toxicity to normal cells and tissues, making them be widely applied in biomedical field. Herein, an approach of combining ion-crosslinking, in-situ reduction and microwave-assisted methods was employed to prepare chitosan-copper-gallic acid nanocomposites (CS-Cu-GA NCs) with dual-functional nano-enzyme characteristics (oxidase- and peroxidase-like functions). The oxidase-like activity of CS-Cu-GA NCs can facilitate the production of hydrogen peroxide (H2O2) when it contacted with physiologically relevant antioxidants (AH2) in bacteria. Subsequently, H2O2 was catalyzed to generate hydroxyl radicals (OH) under the peroxidase-like activity of CS-Cu-GA NCs. Furthermore, CS-Cu-GA NCs integrate the inherent antibacterial properties of chitosan, Cu NPs and Cu2+. Animal experiments revealed that the antibacterial dressing incorporating CS-Cu-GA NCs exhibited its effective promotion of S. aureus-infected wounds healing, as well as no damage to normal tissues. Besides, the antibacterial dressing was prepared to a band aid with excellent water swelling and antibacterial properties, which was further fixed in a medical tape to construct a portable antibacterial product that can be applied to the surface of human skin and showed excellent waterproof performance, providing a new insight for the construction of clinical antibacterial wound healing products.

Production of poly-γ-glutamic acid by a thermotolerant glutamate-independent strain and comparative analysis of the glutamate dependent difference.

Poly-γ-glutamic acid (γ-PGA) is a promising microbial polymer with wide applications in industry, agriculture and medicine. In this study, a novel glutamate-independent γ-PGA producing strain with thermotolerant characteristics was isolated and identified as Bacillus subtilis GXG-5, then its product was also characterized. The fermentation process was optimized by single-factor tests, and results showed that high temperature (50 °C) was especially suitable for the γ-PGA production by GXG-5. The γ-PGA yield reached 19.50 ± 0.75 g/L with substrate conversion efficiency of 78% at 50 °C in 10 L fermentor. Comparison of GXG-5 and GXA-28 (glutamate-dependent strain) under respective optimal fermentation conditions, the γ-PGA yield of GXG-5 was 19.0% higher than that of GXA-28, and GXG-5 was also superior to GXA-28 in the availability of carbon sources and substrates. Furthermore, the glutamate dependent difference between GXA-28 and GXG-5 was analyzed by genomic sequencing, results indicated that genes related to the glutamate dependent difference mainly involved in carbohydrate transport and metabolism and amino acid metabolism, and 13 genes related to γ-PGA synthesis were mutated in GXG-5. This study provided a potential glutamate-independent strain to replace glutamate-dependent strain for γ-PGA production, and shared novel information for understanding the glutamate dependent difference at the genomic level.