Ellagic acid-modified gold nanoparticles to combat multi-drug resistant bacterial infections in vitro and in vivo.

The overuse of antibiotics has led to the rapid development of multi-drug resistant bacteria, making antibiotics increasingly ineffective against bacterial infections. Consequently, there is an urgent need to develop alternative strategies to combat multi-drug-resistant bacterial infections. In this study, gold nanoparticles modified with ellagic acid (EA-AuNPs) were prepared using a simple and mild one-pot hydrothermal process. EA-AuNPs demonstrated high bactericidal efficacy and broad-spectrum antimicrobial activities against clinical isolates of the antibiotic-resistant ESKAPE pathogens. Furthermore, EA-AuNPs effectively disperse biofilms of multi-drug-resistant bacteria. Additionally, EA-AuNPs mitigated inflammatory responses at the bacterial infection sites. The combined bactericidal and anti-inflammatory treatment with EA-AuNPs resulted in faster curing of peritonitis caused by Staphylococcus aureus in mice compared to treatment with free EA or gentamicin. Moreover, transcriptome analysis revealed that EA-AuNPs exhibited a multi-targeting mechanism, making resistance development in pathogens more challenging than traditional antibiotics that recognize specific cellular targets. Overall, EA-AuNPs emerged as a promising antimicrobial agent against multi-drug-resistant bacterial infections.

Dynamic covalent nano-networks comprising antibiotics and polyphenols orchestrate bacterial drug resistance reversal and inflammation alleviation.

New antimicrobial strategies are urgently needed to meet the challenges posed by the emergence of drug-resistant bacteria and bacterial biofilms. This work reports the facile synthesis of antimicrobial dynamic covalent nano-networks (aDCNs) composing antibiotics bearing multiple primary amines, polyphenols, and a cross-linker acylphenylboronic acid. Mechanistically, the iminoboronate bond drives the formation of aDCNs, facilitates their stability, and renders them highly responsive to stimuli, such as low pH and high H2O2 levels. Besides, the representative A1B1C1 networks, composed of polymyxin B1(A1), 2-formylphenylboronic acid (B1), and quercetin (C1), inhibit biofilm formation of drug-resistant Escherichia coli, eliminate the mature biofilms, alleviate macrophage inflammation, and minimize the side effects of free polymyxins. Excellent bacterial eradication and inflammation amelioration efficiency of A1B1C1 networks are also observed in a peritoneal infection model. The facile synthesis, excellent antimicrobial performance, and biocompatibility of these aDCNs potentiate them as a much-needed alternative in current antimicrobial pipelines.

Resveratrol Increases Sensitivity of Clinical Colistin-Resistant Pseudomonas aeruginosa to Colistin In Vitro and In Vivo.

Infections caused by colistin-resistant P. aeruginosa strains pose a serious threat to public health. It is therefore urgent to find new strategies to deal with these bacterial infections. We aimed to investigate the efficacy and mechanisms of the colistin/resveratrol combination in eradicating colistin-resistant P. aeruginosa isolates and their biofilms both in vitro and in vivo. The results revealed that six clinically isolated colistin-resistant P. aeruginosa strains were multidrug resistant (MDR) strains, and resveratrol showed no antimicrobial activity against eight P. aeruginosa strains. Checkerboard assay and time-kill assays indicated that the combination therapy of resveratrol and colistin indicated a remarkable synergistic effect in vitro, and biofilm assays and SEM indicated synergistic antibiofilm activity. Furthermore, this combination could efficiently eliminate MDR bacteria in a murine infection model and improve the survival rate of Galleria mellonella. Fluorescence analysis, ALP, and ß-galactosidase activity test results indicated that the colistin/resveratrol combination increased the membrane permeability of bacteria. In conclusion, our results may provide an efficient alternative pathway against colistin-resistant P. aeruginosa infections. IMPORTANCE P. aeruginosa is a ubiquitous Gram-negative opportunistic pathogen associated with a wide array of life-threatening acute and chronic infections. However, the improper and excessive use of antibiotics has contributed to the increasing emergence of multidrug-resistant (MDR) P. aeruginosa, even colistin-resistant strains, which presents a major challenge to clinical anti-infection treatment. Resveratrol, a naturally occurring polyphenolic antioxidant, can effectively slow down or avoid the occurrence and development of bacterial resistance and is expected to offer a promising strategy to overcome bacterial infections. In this study, colistin/resveratrol combination could synergistically damage the bacterial cell membrane, thereby inducing cell lysis while addressing the emergence of drug resistance. Moreover, this combination therapy may provide an efficient alternative pathway to combat the colistin-resistant P. aeruginosa in clinical practice.

Neighboring Carboxylic Acid Boosts Peroxidase-Like Property of Metal-Phenolic Nano-Networks in Eradicating Streptococcus mutans Biofilms.

Developing nature-inspired nanomaterials with enzymatic activity is essential in combating bacterial biofilms. Here, it is reported that incorporating the carboxylic acid in phenolic/Fe nano-networks can efficiently manipulate their peroxidase-like activity via the acidic microenvironment and neighboring effect of the carboxyl group. The optimal gallic acid/Fe (GA/Fe) nano-networks demonstrate highly enzymatic activity in catalyzing H2 O2 into oxidative radicals, damaging the cell membrane and extracellular DNA in Streptococcus mutans biofilms. Theoretical calculation suggests that the neighboring carboxyl group can aid the H2 O2 adsorption, free radical generation, and catalyst reactivation, resulting in superb catalytic efficiency. Further all-atom simulation suggests the peroxidation of lipids can increase the cell membrane fluidity and permeability. Also, GA/Fe nano-networks show great potential in inhibiting tooth decay and treating other biofilm-associated diseases without affecting the commensal oral flora. This strategy provides a facile and scale-up way to prepare the enzyme-like materials and manipulate their enzymatic activity for biomedical applications.

GOx-encapsulated iron-phenolic networks power catalytic cascade to eradicate bacterial biofilms.

Bacterial biofilms, especially ones caused by multi-drug resistant strains, are increasingly posing a significant threat to human health. Inspired by nature, we report the fabrication of glucose oxidase-loaded iron-phenolic networks that can power the cascade reaction to generate free radicals to eradicate bacterial biofilms. A soft template, sodium deoxycholate, is employed to guarantee glucose oxidase activity during encapsulation, yielding the porous nanocomplexes after removing the template. The porous nature of nanocomplexes, characterized via transmission electron microscopy, N2 adsorption isotherms, and thermogravimetric analysis, facilitates the diffusion of substrates and products during the cascade reaction and protects glucose oxidase from protease attack. Our optimized nanocomplexes (Fe-GA/GOx) could efficiently kill drug-resistant ESKAPE pathogens, including the clinically isolated strains and eradicate their biofilms. In this regard, Fe-GA/GOx could induce over 90% of the biomass of Klebsiella pneumoniae and Staphylococcus aureus biofilms. In the murine peritonitis infection model induced by Staphylococcus aureus and pneumonia model induced by Klebsiella pneumoniae, our Fe-GA/GOx nanocomplexes could efficiently eradicate the bacteria (over 3-log reduction in colony-forming units) and alleviate the inflammatory response without notable side effects on normal tissues. Therefore, our strategy may provide an efficient alternative treatment to combat bacterial biofilms and address the emergence of drug resistance.

Green credit, green reputation, and corporate financial performance: evidence from China.

The article combines green credit and the performance of listed banks in a theoretical and empirical analysis to explore the intrinsic correlation between the two and find the intrinsic motivation for banks to implement green credit. The article first reviews the current status of green credit research and theories related to green development in China and other countries and then analyzes the dynamics of green credit development and value creation, as well as the mechanisms by which green credit improves the financial performance of listed banks. Finally, the article explores the impact of green credit on the financial performance of listed banks through empirical analysis. Through a panel data model, this paper analyzes data related to 19 listed banks in China from 2008 to 2017 to investigate the impact of green credit on the financial performance of listed banks. This study has shown that the green credit ratio, as an indicator of the amount of green credit implemented by listed banks, will positively impact financial performance. But the impact of the current period and the one-period lag is more significant, while the effect of the two-period lag is not significant. The second major finding was that when green reputation is used as an indicator to measure the quality of green credit implementation of listed banks, listed banks' financial performance can be significantly improved. Besides, this study has also found that green credit implementation generally has different impacts on different types of banks.

Universal Antifouling and Photothermal Antibacterial Surfaces Based on Multifunctional Metal-Phenolic Networks for Prevention of Biofilm Formation.

Biofilms formed from the pathogenic bacteria that attach to the surfaces of biomedical devices and implantable materials result in various persistent and chronic bacterial infections, posing serious threats to human health. Compared to the elimination of matured biofilms, prevention of the formation of biofilms is expected to be a more effective way for the treatment of biofilm-associated infections. Herein, we develop a facile method for endowing diverse substrates with long-term antibiofilm property by deposition of a hybrid film composed of tannic acid/Cu ion (TA/Cu) complex and poly(ethylene glycol) (PEG). In this system, the TA/Cu complex acts as a multifunctional building block with three different roles: (i) as a versatile "glue" with universal adherent property for substrate modification, (ii) as a photothermal biocidal agent for bacterial elimination under irradiation of near-infrared (NIR) laser, and (iii) as a potent linker for immobilization of PEG with inherent antifouling property to inhibit adhesion and accumulation of bacteria. The resulted hybrid film shows negligible cytotoxicity and good histocompatibility and could prevent biofilm formation for at least 15 days in vitro and suppress bacterial infection in vivo, showing great potential for practical applications to solve the biofilm-associated problems of biomedical materials and devices.

Dual-Functional Surfaces Based on an Antifouling Polymer and a Natural Antibiofilm Molecule: Prevention of Biofilm Formation without Using Biocides.

Pathogenic biofilms formed on the surfaces of implantable medical devices and materials pose an urgent global healthcare problem. Although conventional antibacterial surfaces based on bacteria-repelling or bacteria-killing strategies can delay biofilm formation to some extent, they usually fail in long-term applications, and it remains challenging to eradicate recalcitrant biofilms once they are established and mature. From the viewpoint of microbiology, a promising strategy may be to target the middle stage of biofilm formation including the main biological processes involved in biofilm development. In this work, a dual-functional antibiofilm surface is developed based on copolymer brushes of 2-hydroxyethyl methacrylate (HEMA) and 3-(acrylamido)phenylboronic acid (APBA), with quercetin (Qe, a natural antibiofilm molecule) incorporated via acid-responsive boronate ester bonds. Due to the antifouling properties of the hydrophilic poly(HEMA) component, the resulting surface is able to suppress bacterial adhesion and aggregation in the early stages of contact. A few bacteria are eventually able to break through the protection of the anti-adhesion layer leading to bacterial colonization. In response to the resulting decrease in the pH of the microenvironment, the surface could then release Qe to interfere with the microbiological processes related to biofilm formation. Compared to bactericidal and anti-adhesive surfaces, this dual-functional surface showed significantly improved antibiofilm performance to prevent biofilm formation involving both Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus for up to 3 days. In addition, both the copolymer and Qe are negligibly cytotoxic, thereby avoiding possible harmful effects on adjacent normal cells and the risk of bacterial resistance. This dual-functional design approach addresses the different stages of biofilm formation, and (in accordance with the growth process of the biofilm) allows sequential activation of the functions without compromising the viability of adjacent normal cells. A simple and reliable solution may thus be provided to the problems associated with biofilms on surfaces in various biomedical applications.

Photothermally Activated Electrospun Nanofiber Mats for High-Efficiency Surface-Mediated Gene Transfection.

Although electrospun nanofibers have been used to deliver functional genes into cells attached to the surface of the nanofibers, the controllable release of genes from nanofibers and the subsequent gene transfection with high efficiency remain challenging. Herein, photothermally activated electrospun hybrid nanofibers are developed for high-efficiency surface-mediated gene transfection. Nanofibers with a core-sheath structure are fabricated using coaxial electrospinning. Plasmid DNA (pDNA) encoding basic fibroblast growth factor is encapsulated in the fiber core, and gold nanorods with photothermal properties are embedded in the fiber sheath composed of poly(l-lactic acid) and gelatin. The nanofiber mats show excellent and controllable photothermal response under near-infrared irradiation. The permeability of the nanofibers is thereby enhanced to allow the rapid release of pDNA. In addition, transient holes are formed in the membranes of NIH-3T3 fibroblasts attached to the mat, thus facilitating delivery and transfection with pDNA and leading to increased proliferation and migration of the transfected cells in vitro. This work offers a facile and reliable method for the regulation of cell function and cell behavior via localized gene transfection, showing great potential for application in tissue engineering and cell-based therapy.

Multistimulus Responsive Biointerfaces with Switchable Bioadhesion and Surface Functions.

Stimuli-responsive biointerfaces can serve as dynamic tools for modulation of biointerfacial interactions. Considering the complexity of biological environments, surfaces with multistimulus responsive switchable bioactivity are of great interest. In the work reported herein, a multistimulus responsive biointerface with on-off switchable bioadhesion (protein adsorption, bacterial adhesion, and cell adhesion) and surface functions in response to change in temperature, pH, or sugar content is developed. This surface is based on a silicon modified with a copolymer containing a thermoresponsive component (poly(N-isopropylacrylamide)) and a component, phenylboronic acid, that can form pH-responsive and sugar-responsive dynamic boronate ester bonds with diol-containing molecules. It is shown that biointeractions including protein adsorption and release, bacteria and cell attachment and detachment on this surface can be regulated by changing temperature, pH, and sugar content of the medium, either individually or all three simultaneously. Furthermore, this surface can switch between two different functions, namely between killing and releasing bacteria, by introduction of a diol-containing biocidal compound. Compared to switchable surfaces that are responsive to only one stimulus, our multistimulus responsive surface is better adapted to respond to the multifunctional complexities of the biological environment and thus has potential for use in numerous biomedical and biotechnology applications.

Smart, Photothermally Activated, Antibacterial Surfaces with Thermally Triggered Bacteria-Releasing Properties.

The development of effective antibacterial surfaces to prevent the attachment of pathogenic bacteria and subsequent bacterial colonization and biofilm formation is critically important for medical devices and public hygiene products. In the work reported herein, a smart antibacterial hybrid film based on tannic acid/Fe3+ ion (TA/Fe) complex and poly(N-isopropylacrylamide) (PNIPAAm) is deposited on diverse substrates. This surface is shown to have bacteria-killing and bacteria-releasing properties based on, respectively, near-infrared photothermal activation and subsequent cooling. The TA/Fe complex has three roles in this system: (i) as a universal adhesive "anchor" for surface modification, (ii) as a high-efficiency photothermal agent for ablation of attached bacteria (including multidrug resistant bacteria), and (iii) as a robust linker for immobilization of NH2-terminated PNIPAAm via either Michael addition or Schiff base formation. Moreover, because of the thermoresponsive properties of the immobilized PNIPAAm, almost all of the killed bacteria and other debris can be removed from the surface simply by lowering the temperature. It is shown that this hybrid film can maintain good antibacterial performance after being used for multiple "kill-and-release" cycles and can be applied to various substrates regardless of surface chemistry or topography, thus providing a broadly applicable, simple, and reliable solution to the problems associated with surface-attached bacteria in various healthcare applications.