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An effective epoxide hydrolase (EH) production strain was mutagenized using 60Co gamma and UV irradiation. Among positive mutant strains, the EH activity of C2-44 reached 33.7 U/g, which was 267% as much as that of the original Aspergillus niger ZJB-09103. Compared with the wild type, there were significant changes in morphology for C2-44, including the color of mycelia on the slants and the shape of conidial head. In addition, glucose and soybean cake were the optimal carbon and nitrogen source in terms of EH activity for the mutant C2-44 instead of soluble starch and peptone for the wild-type strain. The reaction time required to reach 99% enantiomeric excesses of ( S)-epichlorohydrin from racemic substrate was shortened significantly by the mutant C2-44. This phenomenon was probably explained by the higher Vmax for hydrolysis of racemic epichlorohydrin by C2-44 compared with Aspergillus niger ZJB-09103. [ABSTRACT FROM AUTHOR]

( S)-(−)-Ofloxacin and ( R)-(+)-ofloxacin concentrations in the plasma of Pagrosomus major after drug treatment were detected by chiral high-performance liquid chromatography, and various pharmacokinetic parameters were calculated from these data. The elimination half-life of ( S)-(−)-ofloxacin was significantly shorter than that of the ( R)-(+) enantiomer. ( S)-(−)-Ofloxacin also had a significantly lower maximum plasma concentration, area under the concentration-time curve from zero to infinity, and mean residence time than ( R)-(+)-ofloxacin. However, the apparent volume of distribution and total body clearance of ( S)-(−)-ofloxacin were greater than those of ( R)-(+)-ofloxacin. The ratio of the ( S)-(−)- to ( R)-(+)-ofloxacin plasma concentration was always <1.0. Together, these data suggest that ( S)-(−)-ofloxacin was preferentially excreted and ( R)-(+)-ofloxacin was preferentially absorbed. Although the difference in pharmacokinetic parameters was small, the metabolic behavior of the ofloxacin enantiomers in P. major was enantioselective. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Open wounds are prone to bacterial contamination and delayed healing due to environmental exposure, necessitating the development of advanced wound dressings. Hydrogels are ideal candidates for wound care for maintaining a moist environment which benefits for the cell migration and tissue regeneration. However, conventional polysaccharide hydrogels lack intrinsic antibacterial properties, prompting the incorporation of antibacterial agents. Herein, we present a novel composite hydrogel synthesized from curdlan (CUR) and xanthan gum (XG) via thermal annealing, augmented with MXene and Mg2+ to enhance antibacterial efficacy and promote cellular migration. The results proved that the mechanical properties of the composite hydrogel prepared with CUR and XG are significantly enhanced. Due to the influence of near-infrared irradiation, the antibacterial rates of XC/Mg2+/MX against S. aureus and P. aeruginosa are 81.84 % and 89.27 %, respectively. This innovative composite hydrogel offers new insights and avenues in the progress of sophisticated wound healing dressings areas. [ABSTRACT FROM AUTHOR]

Oxidative stress, inflammation, and bacterial infection are critical barriers to wound healing. In this work, a composite wound dressing was designed to promote wound healing and reduce complications. A hydrogel with antibacterial, anti-inflammatory, and antioxidant properties was prepared by crosslinking chitosan (CS) and oxidized konjac glucomannan with Mg2+. We named the prepared hydrogel CPO/Mg2+. The proposed hydrogel demonstrated a significant capacity for promoting wound healing. Experimental results indicate that the CPO/Mg2+ composite hydrogel exhibits a bacteriostatic rate of over 95 % against S. aureus and P. aeruginosa. Furthermore, CPO/Mg2+ reduced oxidative damage to L929 cells in an H 2 O 2 -induced ROS microenvironment and promoted the polarization of macrophage M2. In vivo full-thickness skin defect experiments revealed that the CPO/Mg2+ composite hydrogel enhances collagen deposition and angiogenesis, achieving a closure rate of over 95 % for infected wounds within 14 days. This novel composite hydrogel offers an effective strategy for the repair of infected wounds. [ABSTRACT FROM AUTHOR]

[Display omitted] The combination of chemodynamic therapy (CDT) with photothermal therapy (PTT) is a promising approach to enhance antitumor efficacy of chemotherapeutics. In this paper, we developed novel copper-chelated polydopamine (PDA) nanoparticles (NPs) functionalized with hyaluronic acid (HA) (Cu-PDA-HA NPs) to induce apoptosis and cuproptosis-induced cell death, synergistically combining PTT and CDT. Experimental results revealed that Cu-PDA-HA NPs can respond to excessive glutathione (GSH) and hydrogen peroxide (H 2 O 2) in the tumor microenvironment (TME), which will enable their specific degradation, thereby leading to efficient accumulation of Cu2+ within tumor cells. The released Cu2+ ions were reduced by GSH to generate Cu+, which catalyzed in situ Fenton-like reactions to produce cytotoxic hydroxyl radicals (·OH), disrupting cellular redox homeostasis and promoting apoptosis-related CDT. Meanwhile, the photothermal effect of the Cu-PDA-HA NPs could enhance oxidative stress within the tumor by elevating the temperature and subsequent ·OH production. The enhanced oxidative stress made tumor cells more vulnerable to cuproptosis-induced toxicity. Furthermore, in vivo experiments demonstrated that Cu-PDA-HA NPs can still undergo a temperature increase of 18.9°C following 808 nm near-infrared irradiation (1.0 W/cm2, 5 min). Meanwhile, Cu-PDA-HA NPs were able to induce oligomerization of dihydrolipoamide S-acetyltransferase (DLAT) and down-regulate Fe-S cluster proteins such as ferredoxin (FDX1), thereby activating cuproptosis. Therefore, this study provides a novel approach for designing multifunctional nanoparticles with on-demand Cu2+ release and offers a fresh perspective for exploring synergistic therapeutic strategies involving CDT/PTT/apoptosis/cuproptosis. [ABSTRACT FROM AUTHOR]

[Display omitted] Open wounds are susceptible to bacterial infections, and antibiotics are commonly used to treat these infections. However, widespread use of antibiotics will easily induce bacterial resistance. Green antibacterial agents serve as excellent alternative for antibiotics in infection therapy. In this work, polydopamine (PDA) was used to modify the surface of ZIF-8, which not only enhances the water stability of Zeolitic imidazolate framework-8(ZIF-8) but also improves its photocatalytic and photothermal capabilities. ZIF-8@PDA was incorporated into carboxylated chitosan (CCS) films as an antibacterial agent, the resulting ZIF-8@PDA-CCS films exhibit excellent ionic/photocatalytic/photothermal antibacterial performance. The film exhibited an impressive 99% in vitro bacterial inhibition rate. After treatment with ZIF-8@PDA-CCS, the bacteria in infected wounds can be completely suppressed. These findings suggest that ZIF-8@PDA-CCS could serve as a potentional antibacterial dressing. [ABSTRACT FROM AUTHOR]

[Display omitted] Disulfiram (DSF) metabolites exhibit antitumor properties when bound to Cu2+. This combination also promotes the generation of reactive oxygen species (ROS), ultimately leading to tumor cell death. In this study, CuO 2 served as a carrier for DSF, forming a dual-drug delivery system with Cu2+ and DSF encapsulated in polydopamine (PDA). In the final delivery system, CuO 2 (DSF-CuO 2 @PDA) was hydrolyzed at the tumor site, releasing both Cu2+ and H 2 O 2. Cu2+ reacts with DSF metabolites to form Bis(diethyldithiocarbamate)-Cu (CuET), which triggers a Fenton-like reaction that generates ROS. Chemotherapy and chemodynamic therapy exhibited significant tumor-suppressive capabilities, with an inhibition rate of 61 %. In addition, the DSF-CuO 2 @PDA complex demonstrated superlative tumor-targeting ability and biocompatibility. [ABSTRACT FROM AUTHOR]

[Display omitted] The Cu2+ complex formed by the coordination of disulfiram (DSF) metabolite diethyldithiocarbamate (DTC), Cu(DTC) 2 , can effectively inhibit tumor growth. However, insufficient Cu2+ levels in the tumor microenvironment can impact tumor-suppressive effects of DTC. In this study, we proposed a Cu2+ and DSF tumor microenvironment-targeted delivery system. This system utilizes hollow mesoporous silica (HMSN) as a carrier, after loading with DSF, encases it using a complex of tannic acid (TA) and Cu2+ on the outer layer. In the slightly acidic tumor microenvironment, TA/Cu undergoes hydrolysis, releasing Cu2+ and DSF, which further form Cu(DTC) 2 to inhibit tumor growth. Additionally, Cu2+ can engage in a Fenton-like reaction with H 2 O 2 in the tumor microenvironment to form OH, therefore, chemodynamic therapy (CDT) and Cu(DTC) 2 are used in combination for tumor therapy. In vivo tumor treatment results demonstrated that AHD@TA/Cu could accumulate at the tumor site, achieving a tumor inhibition rate of up to 77.6 %. This study offers a novel approach, circumventing the use of traditional chemotherapy drugs, and provides valuable insights into the development of in situ tumor drug therapies. [ABSTRACT FROM AUTHOR]

[Display omitted] Nanodrug delivery systems (NDSs), such as mesoporous silica, have been widely studied because of their high specific surface area, high loading rate, and easy modification; however, they are not easily metabolized and excreted by the human body and may be potentially harmful. Hence, we aimed to examine the synergistic anti-tumor effects of ex vivo chemo-photothermal therapy to develop a rational and highly biocompatible treatment protocol for tumors. We constructed a biodegradable NDS using organic mesoporous silica with a tetrasulfide bond structure, copper sulfide core, and folic acid-modified surface (CuS@DMONs-FA-DOX-PEG) to target a tumor site, dissociate, and release the drug. The degradation ability, photothermal conversion ability, hemocompatibility, and in vitro and in vivo anti-tumor effects of the CuS@DMONs-FA-DOX-PEG nanoparticles were evaluated. Our findings revealed that the nanoparticles encapsulated in copper sulfide exhibited significant photothermal activity and optimal photothermal conversion rate. Further, the drug was accurately delivered and released into the target tumor cells, annihilating them. This study demonstrated the successful preparation, safety, and synergistic anti-tumor effects of chemo-photothermal therapeutic nanomaterials. [ABSTRACT FROM AUTHOR]

In the realm of natural polysaccharides, hydrogen bonding is a prevalent feature, yet its role in enhancing photocatalytic antimicrobial properties has been underexplored. In this paper, heterojunctions formed by graphene oxide (GO) and ZIF-8 were locked in sodium alginate/ carboxylated cellulose nanocrystals via hydrogen bonding networks, designated as SCGZ. The SCGZ films exhibit superior photocatalytic performance compared to either ZIF-8 or heterojunctions. This enhancement is primarily due to two key factors: firstly, the hydrogen bonding network significantly enhances the transfer of protons and holes, thereby improving the separation efficiency of photo-generated carriers; secondly, the hydrogen bonding between the layers facilitates a more efficient charge transfer, which expedites the movement of electrons from ZIF-8 to GO upon illumination. In vitro studies demonstrated that the SCGZ films possess remarkable antibacterial capabilities, achieving 99.75 % and 99.61 % inhibition rates against S. aureus and E. coli , respectively. In vivo animal experiments have shown that SCGZ films can significantly accelerate the healing process of damaged tissues, with a healing efficiency of up to 90.5 %. This research provides additional insights into the development of natural polysaccharide-based multi‑hydrogen bonded macromolecules with enhanced photocatalytic properties. [Display omitted] [ABSTRACT FROM AUTHOR]

• A cerium dioxide nanozyme doped hybrid hydrogel was prepared for diabetic wound healing. • The proposed hydrogel exhibits antioxidant and antibacterial abilities. • The hybrid hydrogel can reshape the wound microenvironment by consuming ROS and inhibiting infection. • The hybrid hydrogel can effectively promote the healing of infected diabetic wounds. Diabetic wounds are among the most severe chronic complications in patients with diabetes. Owing to the detrimental effects of high glucose and high levels of reactive oxygen species (ROS) in the wound microenvironment, diabetic wound healing is significantly challenging. To address the issues of elevated ROS levels and infection susceptibility in diabetic wounds, we designed a composite hydrogel system loaded with cerium dioxide nanoparticles (CeO 2 NPs) and vancomycin. This hydrogel aimed to reshape the wound microenvironment by continuously consuming ROS and inhibiting infection. Experimental results demonstrated that the CeO 2 NPs-loaded hydrogel demonstrated an 85.40% clearance rate of hydroxyl radicals (·OH) and achieved over 90% inhibition against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), and effectively promoted the healing of diabetic mouse wounds. This cerium dioxide nanozyme hybrid hydrogel system can exert antioxidative and antibacterial effects and serve as a wound dressing to promote the healing of infected diabetic wounds. [ABSTRACT FROM AUTHOR]

Ferroptosis, as an effective sensitizer for apoptosis-based cancer treatments, has been elucidated to rely on high levels of intracellular oxidative stress mediated by the accumulation of reactive oxygen species (ROS). However, ferroptosis-related oxidation effect is largely counteracted by the endogenous reductive glutathione (GSH). Here, we constructed a self-assembled metal-organic nanomedicine p53/Ce6@ZF-T, which was composed of p53 plasmid-complexed chlorin e6 (Ce6)-poly(amidoamine), Fe2+-containing mesoporous zeolitic imidazolate framework-8 and naturally derived tannic acid (TA). The highly cytotoxic ROS was continuously produced via Fe2+-mediated and TA-assisted enhanced Fenton reaction as well as Ce6-induced photosensitive reaction, and meanwhile, the intratumoral upregulated p53 expression inactivated glutathione peroxidase 4 (GPX4) to suppress lipid peroxidation (LPO) resistance, thus resulting in amplified oxidative stress and intensified ferroptosis-apoptosis therapy. The notable anticancer efficacy of p53/Ce6@ZF-T both in vitro and in vivo substantially evidenced the high feasibility of oxidative stress-amplified therapeutic modality for enhanced ferroptosis-apoptosis combined therapy, which would be a promising approach in the field of cancer treatment in the future. p53-mediated ferroptosis could remodel the sensitivity of tumors to proapoptotic therapy for intensified ferroptosis-apoptosis combined tumor therapy through an oxidative stress-amplified nanomedicine p53/Ce6@ZF-T. [Display omitted] • An oxidative stress-amplified nanomedicine (p53/Ce6@ZF-T) was designed for inducing ferroptosis-apoptosis antitumor therapy. • p53/Ce6@ZF-T combined Fenton reaction with photodynamic therapy to generate abundant highly cytotoxic ROS. • Tannic acid coating on p53/Ce6@ZF could strengthen Fenton reaction efficacy by accelerating the conversion of Fe3+ to Fe2+. • p53/Ce6@ZF-T showed an excellent expression ability of p53 protein to inactivate GPX4 activity and amplify ferroptosis. [ABSTRACT FROM AUTHOR]

Mesoporous silica nanoparticles (MSN) are effective drug delivery carriers because of their adjustable large pore size and high porosity. In this study, complex nanoparticles containing disulfide bonds (SS) were designed and prepared as curcumin (Cur) carriers by using fucoidan (FUC) and MSN as the polymer matrix. The product was characterized using scanning electron microscopy, transmission electron microscopy, dynamic light scattering, Fourier-transform infrared spectroscopy, and an N 2 adsorption and desorption test. When the mass ratio of MSN to FUC was 2:1, the nanospheres particle size was the smallest (295.6 ± 0.98 nm, −35.2 ± 0.8 mV). Furthermore, the curcumin encapsulation rate by MSN-Cur-SS-FUC was over 90%, and the cumulative release rate in 24 h was over 80% due to the combined effect of weak acidity and high glutathione concentration in the tumor site microenvironment. When the Cur concentration was 50 μg/mL, the cell viability of free Cur was 63.8%, the cell viability of MSN-Cur-SS-FUC was 14.5%, and the cell viability of MSN-SS-FUC at the same concentration remained above 74.6%. MSN-SS-FUC composite nanoparticles showed a good delivery of Cur, a lipid-soluble active compound, and provides a new delivery route for other lipid-soluble and poorly bioavailable active compounds. [ABSTRACT FROM AUTHOR]

In this study, zein and fucoidan-based composite nanoparticles were prepared by the antisolvent precipitation method. The effects of different calcium ion (Ca2+, 0–3.0 mM) concentrations on the stability of the composite nanosystems loaded with quercetin were studied under different conditions (pH, temperature, salt concentration, and ultraviolet light irradiation), and the composite nanoparticles were characterized. Electrostatic interactions, hydrogen bonding, and hydrophobic interactions are the main forces underlying the formation of composite nanoparticles. The addition of Ca2+ led to improved release of the active substances from the composite nanoparticles in simulated digestive solutions (especially when the Ca2+ concentration was 1.5 mM). The composite nanosystems based on alcohol-soluble proteins and anionic polysaccharides with added Ca2+ can be potentially applied for the delivery of active substances. [ABSTRACT FROM AUTHOR]

The high expression of reduced glutathione (GSH) and low pH in tumor sites have encouraged new ideas for targeted drug release. The tumor microenvironment is a crucial target for studying the anti-tumor efficiency of photothermal therapy because the microenvironment plays a key role in cancer progression, local resistance, immune escaping, and metastasis. Herein, active mesoporous polydopamine nanoparticles loaded with doxorubicin and functionalized with N,N′ -bis(acryloyl)cystamine (BAC) and cross-linked carboxymethyl chitosan (CMC) were used to induce simultaneous redox- and pH-sensitive activity to achieve photothermal enhanced synergistic chemotherapy. The inherent disulfide bonds of BAC were able to deplete glutathione, thus increasing the oxidative stress in tumor cells and enhancing the release of doxorubicin. Additionally, the imine bonds between CMC and BAC were stimulated and decomposed in the acidic tumor microenvironment, improving the efficiency of light conversion through exposure to polydopamine. Moreover, in vitro and in vivo investigations demonstrated that this nanocomposite exhibited improved selective doxorubicin release in conditions mimicking the tumor microenvironment and low toxicity towards non-cancerous tissues, suggesting there is high potential for the clinical translation of this synergistic chemo-photothermal therapeutic agent. [ABSTRACT FROM AUTHOR]

A hemostatic sponge should perform rapid hemostasis and exhibit antibacterial properties, whilst being non-toxic, breathable, and degradable. This study prepared a hemostatic sponge (CQTC) with microchannels, specifically a microchannel structure based on quaternized chitosan (QCS) and carboxylated cellulose nanofibers (CCNF) obtained by using tannic acid and Cu2+ complex (crosslinking agent). The sponge had low density and high porosity, while being degradable. The combination of microchannels and three-dimensional porous structure of CQTC leads to excellent liquid absorption and hemostasis ability, based on a liquid absorption rate test and in vitro hemostasis experiment. In addition, CQTC exhibited excellent antibacterial activity against both gram-negative and gram-positive bacteria, and it promoted wound healing. In conclusion, this porous and microchannel hemostatic sponge has broad application prospects as a clinical wound hemostatic material. • A microchannel quaternized chitosan and carboxylated cellulose nanofiber sponge was prepared. • The microchannel sponge showed excellent hemostatic properties in vitro and in vivo. • The prepared sponge exhibited excellent antibacterial activity in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Infection represents a major clinical barrier that delays wound healing, while the overuse of antibiotics can lead to bacterial resistance. Hence, it is of particular important to develop a new type of dressing to combat bacterial resistance. Herein, a carbon nitride-polydopamine‑silver complex (C 3 N 4 -PDA-Ag) was prepared using the photocatalyst C 3 N 4 and silver nanoparticles (Ag NPs) to achieve a synergistic antimicrobial effect. The solution casting method was then employed to further modify the C 3 N 4 -PDA-Ag complex by compounding it with chitosan (CS), thereby forming a C 3 N 4 -PDA-Ag@CS film. The results revealed that the C 3 N 4 -PDA-Ag@CS film exhibits superior antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa compared to the CS group. The hemolysis, cytotoxicity, and in vivo implantation experiments indicated that the composite film possesses excellent in vitro and in vivo biocompatibility. In addition, the composite dressing promoted wound healing in infected mice by facilitating collagen deposition and accelerating epidermal regeneration. Collectively, the findings of this study clearly demonstrate that the C 3 N 4 -PDA-Ag@CS composite dressing has excellent antibacterial properties, biocompatibility, and enhances wound healing, thus providing a strategy for the application of photocatalytic materials for the treatment of infected wounds. [Display omitted] [ABSTRACT FROM AUTHOR]

• Nanoparticles conjugated with DOX and COS via DF-PEG-DF. • Nanoparticles showed significant pH sensitivity on in vitro release assays. • Introduction of COS increases the biocompatibility and solubility of DOX. • Nanoparticles have a good potential as lipid-soluble drug carriers. In this study, we developed pH-sensitive chito-oligosaccharide nano-drug-loaded particles with good biocompatibility, biodegradation, and controlled drug delivery. Chitosan oligosaccharides (COS), Doxorubicin (DOX) amino groups, and aromatic aldehydes of benzaldehyde-terminated polyethylene glycol were used to spontaneously form pH-sensitive aniline bonds. We aimed to achieve site targeting under weak acidic tumor conditions, improve the efficacy, and reduce the toxic side effects of the drug. Particle size, drug encapsulation efficiency, loading efficiency, and zeta potential of nanoparticles were optimized by altering the ratios of aldehyde, amino groups, and sodium tripolyphosphate. The drug encapsulation efficiency and loading efficiency of COS-DOX1 were 5.55 ± 0.13% and 88.81 ± 2.00%, respectively, and the in vitro drug release process displayed a specific pH responsiveness. Co-culture of COS-DOX with HCT-116 human colon cancer cells showed that the nanoparticles exhibited dose-dependent cytotoxicity. At a low dose, COS-DOX1 can promote DOX uptake of tumor cells and exhibit higher cytotoxicity than DOX alone. [ABSTRACT FROM AUTHOR]

Asymmetric sponge dressings with a hydrophobic surface and a hydrophilic inner layer can prevent bacterial infiltration and ensure efficient absorption of wound exudate. In this work, ε-polylysine/aliphatic polyurethane sponge (EPU) was prepared by prepolymer foaming process, and oxidized hyaluronic acid (OHA) was cross-linked with ε-polylysine (EPL) in EPU through schiff-base reaction to obtain EHPU. Octaisobutyl polyhedral oligomeric silsesquioxane (Oi-POSS) was uniformly sprayed onto the surface of EHPU as the hydrophobic layer, resulting in asymmetric sponge dressings denoted as P-EHPU. These dressings demonstrate capabilities in resisting staining and bacterial invasion, with internal EPL effectively inhibiting bacterial proliferation on the wound surface. The introduction of OHA and EPL leads to a denser and more complete pore structure of the sponge, endowing it with good compression, tensile strength, and hemostatic performance. Wound healing studies indicate that P-EHPU effectively prevents external bacterial infiltration and promotes wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Porous microsphere hemostatic materials, which possess rapid hemostatic, antibacterial, and wound healing-promotion properties, have key advantages over hemostatic dressings with a single hemostatic function. Using rod-shaped cellulose nanocrystals as the supporting framework, sodium alginate/cellulose nanocrystal porous microspheres (SA/CNC) were prepared using an inverse emulsion method. After SA/CNC self-assembly with the antibacterial polymer ε-polylysine, the hemostatic porous microspheres (PSLMs) showed high porosity, high liquid absorption capacity, and excellent coagulation properties. The in vitro and in vivo coagulation properties of PSLMs were evaluated and compared with those of the commercially available chitosan hemostatic powder. PSLMs had marked hemostatic effects in the following mouse hemorrhage models: caudal (81.20 s), liver (48.44 s), and femoral artery (71.66 s). After the introduction of ε-polylysine with excellent antibacterial properties to PSLMs, PSLMs effectively inhibited the activities of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa., (Copyright © 2022 Elsevier Ltd. All rights reserved.)