Bacterial Microenvironment Research Articles

Coordination-Driven in Situ Grown Copper Peroxide in Mesoporous Dopamine with Self-Supplied H2O2 for Synergistic Enhanced PTT/CDT Antibacterial Treatment and Wound Healing.

As antibiotic resistance increases, alternative antimicrobial methods become essential. Chemical dynamics therapy (CDT) utilizing copper peroxide (CuO2) nanodots shows significant potential in antibacterial applications due to its ability to self-supply hydrogen peroxide (H2O2) on its own. This characteristic effectively addresses the challenges of low H2O2 levels and high glutathione (GSH) expression in the bacterial infection microenvironment. However, its tendency to aggregate and instability greatly affect its effectiveness. Therefore, this study developed a coordination-driven strategy to prepare copper peroxide-loaded mesoporous polydopamine nanomaterials (CuO2@MPDA) through in situ growth of CuO2 in mesoporous polydopamine utilizing the chelating interaction between amino and catechol structures of MPDA with copper ions. This strategy not only ensures that copper peroxide is evenly distributed within the pores of mesoporous polydopamine but also protects it through the shielding effect of pores, greatly enhancing its dispersibility and stability. More notably, the loading of CuO2 enhances the photothermal performance of MPDA by broadening its light absorption range, and MPDA-mediated photothermal therapy (PTT) can accelerate CuO2 to produce more hydroxyl radicals by speeding up chemical reactions, resulting in a combined boost in PTT and CDT. The developed CuO2@MPDA nanomaterials at very low concentrations exhibit improved antibacterial efficiency both in vitro and in vivo. Overall, this study provides an innovative strategy to construct an antibacterial nanoplatform for synergistically enhanced PTT/CDT dual-mode antibacterial treatment, exhibiting great potential for future biomedical applications.

Engineering Robust Silver-Decorated calcium peroxide Nano-Antibacterial Platforms for chemodynamic enhanced sterilization

Calcium peroxide (CaO2) is commonly used as a hydrogen peroxide (H2O2) donor to eliminate bacterial infections. However, the rapid dissociation of CaO2 and the explosive release of H2O2 have limited the development of CaO2 in the antibacterial field. Therefore, a series of silver nanoparticles (AgNPs) functionalized bacteria-triggered smart hydrogels (CSA-H) that integrate sustained release of nanoparticles and localized chemodynamic sterilization were constructed. The pH-responsive hydrogel formed through the Schiff base reaction enables the responsive release of CaO2 nanoparticles while simultaneously regulating the concentration of H2O2 within the bacterial infection microenvironment. AgNPs are capable of reacting with H2O2 under mildly acidic conditions to produce hydroxyl radicals with enhanced antimicrobial activity. The antimicrobial results demonstrated that AgNPs functionalized silicon dioxide-coated calcium peroxide (CaO2@SiO2/AgNPs) nanoparticles exhibited enhanced bactericidal activity compared to AgNPs or CaO2 alone. Furthermore, CSA-H hydrogels exhibited significant antibacterial activity against S. aureus and E. coli under the dual effect of AgNPs and pH-driven Fenton-like reactions. This chemodynamic antibacterial platform is environmentally responsive and provides a promising strategy for creating multifunctional hydrogels loaded with nano-enzymes, thus advancing the development of AgNPs in chemodynamic-antibacterial related applications.

A triple-mode strategy combining low-temperature photothermal, photodynamic, and chemodynamic therapies for treating infectious skin wounds.

The skin is the first natural barrier of the human body. Bacterial infections severely hinder the healing process of skin wounds and pose a great threat to human health. Therefore, it is particularly urgent to develop new antimicrobial strategies for bacterial pathogen clearance and wound healing. In this study, a metal-organic framework (MOF), Fe-MIL88B-NH2, was incorporated with the photosensitizer indocyanine green (ICG) to construct composite nanoparticles (MOF@ICG NPs) with multiple antibacterial activities. Under mild near-infrared (NIR) irradiation, the photosensitizer ICG in the MOF@ICG NPs undergoes photothermal conversion (∼45 °C) and photodynamic reactions to generate heat and singlet oxygen (1O2). In addition, the Fenton reaction of the NPs with hydrogen peroxide (H2O2) in the bacterial infection microenvironment resulted in the generation of hydroxyl radicals (˙OH), thus achieving the three-mode combination of low-temperature photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT). The in vitro experimental results showed that MOF@ICG MPs had excellent antibacterial properties and good cytocompatibility, with some ability to promote the migration of L-929 fibroblasts. Furthermore, under NIR irradiation, MOF@ICG NPs could significantly kill bacteria and promote skin wound healing according to the results of animal experiments. The wound healing rate reached 87.1% after 7 days of treatment. The research results break through the limitations of single-mode antibacterial technology and provide certain theoretical guidance and technical support for the research and development of new antibacterial materials.

Redox-responsive degradation of antimicrobials with programmable drug release for enhanced antibacterial activity

The global crisis of antibiotic resistance has impelled the exigency to develop more effective drug delivery systems for the treatment of bacterial infection. The development of possessing high biocompatibility and targeted delivery of antimicrobials remains a persisting challenge. For programmable release of efficient antimicrobials in infection sites to enhance antibacterial activity, herein, we fabricated diselenide-bridged mesoporous organosilica nanoparticle-supported silver nanoparticles (Ag NPs) with high drug-loading capacity for the co-delivery of tobramycin (TOB) within one drug delivery system (Ag-MON@TOB (Se)). The resultant Ag-MON@TOB (Se) exhibited favorable biocompatibility due to its high stability in the physiological condition. Notably, such Ag-MON@TOB (Se) manifested a programmable structural destabilization to trigger sequential drug release in response to the oxidative stimuli within the bacterial infection microenvironment. In contradistinction to the oxidation-stable disulfide bond moieties within the framework of the nanocarrier (Ag-MON@TOB (S)), the Ag-MON@TOB (Se) with its programmed drug release behavior augmented prominent antibacterial therapy both in vitro and in vivo. This work represents a promising strategy for programmable drug release by harnessing a responsive degradable vehicle to enhance the treatment of bacterial infection.

Xuanfei Baidu decoction ameliorates bleomycin-elicited idiopathic pulmonary fibrosis in mice by regulating the lung-gut crosstalk via IFNγ/STAT1/STAT3 axis

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial pneumonia, the available treatment option is limited because the etiology and pathological process are not well understood. Although gut-lung axis reported with an emerging area of host-associated microbiota exist in many chronic lung diseases, the connection between gut-lung microbiota composition with in-site inflammation in IPF development is not yet established. PurposeWe aimed to address the microbiota and immunity connection, and make it clear how a listed drug, Xuanfei Baidu Decoction (XFBD) affect the lung-gut crosstalk for IPF amelioration, which was previously reported for restoring disrupted lung in IPF and protecting intestinal injury. MethodsFirstly, Micro-CT (μCT) and histopathology were used to check for pathological changes in the lungs and intestines of bleomycin (BLM)-induced IPF mice. Then, Reverse Transcription and Quantitative Real-time PCR (RT-qPCR) and Western blot (WB) assays were employed to detect the integrity of the barrier of lungs and intestines in IPF mice. Subsequently, flow cytometry and 16S rRNA sequencing were used to evaluate the immune and microbial microenvironment of the lungs and intestines. We analyzed the lung-gut microbiota crosstalk for further mechanism exploration. ResultsFirstly, we revealed that XFBD protected the integrity of the lung and intestinal barriers in the IPF mice, as evidenced by the up-regulation of ZO-1, Claudin-1, Occludin, and VE Cadherin protein expression. Then, we analyzed the changing microbiota and T cell in the gut-lung axis in IPF, and with XFBD, six highly relevant microenvironments were demonstrated that crossing damaged lung-gut barriers and XFBD could reverse these chaotic bacterial and immunity micro-environment, among them Akkermansia was an essential bacteria affecting the expression of systemic IFN-γ downstream STAT1/STAT3 axis was also studied. XFBD prominently up-regulated the production of IFN-γ and p-STAT1 and down-regulated p-STAT3, consequently exerting effects on the lung barrier and gut barrier. Taken together, XFBD ameliorated BLM-induced IPF mice by regulating IFNγ/STAT1/STAT3 axis. ConclusionAltogether, our results revealed that XFBD improved the BLM-elicited IPF mice by regulating gut-lung crosstalk via IFN-γ/STAT1/STAT3 axis and provided a new insight of gut-lung crosstalk in IPF, especially the dynamic changes of microorganisms in the damaged lungs needed to pay more attention during IPF therapy.

Nitrite reductase-mimicking catalysis temporally regulating nitric oxide concentration gradient adaptive for antibacterial therapy.

The unique bacterial infection microenvironment (IME) usually requires complicated design of nanomaterials to adapt to IME for enhancing antibacterial therapy. Here, an alternative IME adaptative nitrite reductase-mimicking nanozyme is constructed by in situ growth of ultrasmall copper sulfide clusters on the surface of a nanofibrillar lysozyme assembly (NFLA/CuS NHs), which can temporally regulate nitric oxide (NO) gradient concentration to kill bacteria initially and promote tissue regeneration subsequently. Benefiting from a copper nitrite reductase (CuNIR)-inspired structure with CuS cluster as active center and NFLA as skeleton, NFLA/CuS NHs efficiently boost the catalytic reduction of nitrite to NO. The inherent supramolecular fibrillar networks displays excellent bacterial capture capability, facilitating initial high-concentration NO attacks on the bacteria. The subsequent catalytic release of low-concentration NO by NFLA/CuS NHs-mediated nitrite reduction remarkably promotes cell migration and angiogenesis. This work paves the way for dynamically eliminating MDR bacterial infection and promoting tissue regeneration in a simple and smart way through CuNIR-mimicking catalysis.

Zinc finger-inspired peptide-metal-phenolic nanointerface enhances bone-implant integration under bacterial infection microenvironment through immune modulation and osteogenesis promotion

Orthopedic and dental implantations under bacterial infection microenvironment face significant challenges in achieving high-quality bone-implant integration. Designing implant coatings that incorporate both immune defense and anti-inflammation is difficult in conventional single-functional coatings. We introduce a multifunctional nanointerface using a zinc finger-inspired peptide-metal-phenolic nanocoating, designed to enhance implant osseointegration under such conditions. Abaloparatide (ABL), a second-generation anabolic drug for treating osteoporosis, can be integrated into the design of a zinc-phenolic network constructed on the implant surface (ABL@ZnTA). Importantly, the phenolic-coordinated Zn2+ ions in ABL@ZnTA can act as zinc finger motif to co-stabilize the configuration of ABL through multiple molecular interactions, enabling high bioactivity, high loading capacity (1.36 times), and long-term release (>7 days) of ABL. Our results showed that ABL@ZnTA can modulate macrophage polarization from the pro-inflammatory M1 towards the anti-inflammatory M2 phenotype, promoting immune osteogenesis with increased OCN, ALP, and SOD 1 expression. Furthermore, the ABL@ZnTA significantly reduces inflammatory fibrous tissue encapsulation and enhances the long-term stability of the implants, indicated by enhanced binding strength (6 times) and functional connectivity (1.5−3 times) in the rat bone defect model infected by S. aureus. Overall, our research offers a nano-enabled synergistic strategy that balances infection defense and osteogenesis promotion in orthopedic and dental implantations.

Thermal-Responsive Antibacterial Hydrogel with Photothermal Therapy and Improving Wound Microenvironment for Promote Healing.

Skin damage is one of the most prevalent human injuries, which affects the health of human beings. However, skin damage is often accompanied by bacterial infection and wound microenvironment changes, causing damage to normal cells and inhibiting wound healing. Herein, we designed a thermal-responsive antibacterial hydrogel (GAG hydrogel) loaded with catalase (CAT)-like Au@Pt@MgSiO3 nanoparticles (APM NPs) and gentamicin (GM) to promote wound healing. The GAG hydrogel was used in a photothermal therapy (PTT)/antibiotic combination to kill bacteria, reduce the use of antibiotics, improve the wound microenvironment, promote cell proliferation, and accelerate wound healing. Under near-infrared laser irradiation, APM NPs in the hydrogel generated local hyperthermia to kill bacteria. Meanwhile, the generated heat led to a change in the hydrogel's morphology, enabling it to release GM and APM NPs to prevent the overuse of antibiotics. Subsequently, the CAT-like ability of the APM NPs decreased the oxidative stress caused by hydrogen peroxide (H2O2), thus remodeling the wound microenvironment. Then, the weakly acidic microenvironment of the wound caused the decomposition of the APM NPs and the release of magnesium ions (Mg2+), promoting the growth and migration of cells for wound healing. Therefore, the studied thermal-responsive antibacterial (GAG) hydrogel has potential in the field of wound healing.

Living Bacteriophage Engineering for Functional Material Synthesis, Bioanalytical Sensing and Disease Theranostics

Facing the increasingly global crisis of antibiotic resistance, it is urgent to develop new antibacterial agents and methods. Simultaneously, as research progresses, the occurrence, development, and treatment of diseases, especially some malignant cancers, are found to be closely associated with the bacterial microenvironment, prompting us to reconsider the efficiency of existing antibacterial strategies for disease treatments. Bacteriophages have been employed as antibacterial agents for an extended period owing to their high biocompatibility and particular targetability toward the host bacterial strains. Nonetheless, they are almost neglected due to their slow and limited efficacy in antibacterial practice, especially in acute and severe infectious cases. In recent years, fantastic advancements in various biochemical technologies, such as bacteriophage display technology, genetic engineering, and chemical molecular engineering, have enabled scientists to conduct a broader range of modifications and transformations on the existing bacteriophages with inherited unique characteristics of themselves. As a result, a series of novel bacteriophage platforms are designed and fabricated with significantly enhanced properties and multiplied functionalities. These offer new avenues for combating infections caused by drug-resistant bacteria and treatment of malignancies that are associated with bacterial infections, holding great significance and potential in the innovative theranostic applications.

Real-Time pH Sensor in Bacterial Microenvironments Using Liquid Crystal Core-Shell Microspheres.

It is well-known that the bacterial microenvironment imposes restrictions on the growth and behavior of bacteria. The localized monitoring of microenvironmental factors is appreciated when consulting bacterial adaptation and behavior in the presence of chemical or mechanical stimuli. Herein, we developed a novel liquid crystal (LC) biosensor in a microsphere configuration for real-time 3D monitoring of the bacteria microenvironment, which was implemented by a microfluidic chip. As a proof of concept, a LC gel (LC-Gel) microsphere biosensor was prepared and employed in the localized pH changes of bacteria by observing the configuration change of LC under polarized optical microscopy. Briefly, the microsphere biosensor was constructed in core-shell configuration, wherein the core contained LCE7 (a nematic LC) doped with 4-pentylbiphenyl-4'-carboxylic acid (PBA), and the shell encapsulated the bacteria. The protonation of carboxyl functional groups of the PBA induced a change in charge density on the surface of LCE7 and the orientation of E7 molecules, resulting in the transitions of the LC nucleus from axial to bipolar. The developed LC-Gel microspheres pH sensor exhibited its dominant performance on localized pH real-time sensing with a resolution of 0.1. An intriguing observation from the prepared pH biosensor was that the diverse bacteria impelled distinct acidifying or alkalizing effects. Overall, the facile LC-Gel microsphere biosensor not only provides a versatile tool for label-free, localized pH monitoring but also opens avenues for investigating the effects of chemical and mechanical stimuli on cellular metabolism within bacterial microenvironments.

Injectable Therapeutic Hydrogel with H2O2 Self-Supplying and GSH Consumption for Synergistic Chemodynamic/Low-Temperature Photothermal Inhibition of Postoperative Tumor Recurrence and Wound Infection.

Postoperative tumor recurrence and wound infection remain significant clinical challenges in surgery, often requiring adjuvant therapies. The combination treatment of photothermal therapy (PTT) and chemodynamic therapy (CDT) has proven to be effective in cancer treatment and wound infection. However, the hyperthermia during PTT increases the risk of normal tissue damage, severely impeding its application. Moreover, the efficacy of CDT is limited by insufficient hydrogen peroxide (H2O2) and excessive glutathione (GSH) levels at tumor or infection sites. Herein, an injectable and multifunctional CuO2@Au hydrogel system (CuO2@Au Gel) is developed for synergistic CDT and low-temperature PTT (LTPTT) to prevent tumor recurrence and bacterial wound infections. CuO2@Au Gel is constructed by embedding therapeutic CuO2@Au into low-melting point agarose hydrogel. In vitro and in vivo experiments confirm that the CuO2@Au in CuO2@Au Gel is capable of self-supplying H2O2 and depleting GSH, exhibiting effective CDT effect in acidic tumor or bacterial infected microenvironment. Additionally, it exhibits favorable photothermal conversion ability, inducing localized temperature elevation and synergistically enhancing CDT efficiency. The prepared CuO2@Au Gel demonstrates efficient tumor ablation capability in post-surgery recurrence mouse models and exhibits promising anti-infective efficiency in bacterial infection wound models, indicating significant potential in adjuvant therapy for post-surgical treatment and recovery.

Dual pH- and ATP-Responsive Antibacterial Nanospray: On-Demand Release of Antibacterial Factors, Imaging Monitoring, and Accelerated Healing of Bacteria-Infected Wounds under NIR Activation.

The prevalence of pathogenic bacterial infections with high morbidity and mortality poses a widespread challenge to the healthcare system. Therefore, it is imperative to develop nanoformulations capable of adaptively releasing antimicrobial factors and demonstrating multimodal synergistic antimicrobial activity. Herein, an NIR-activated multifunctional synergistic antimicrobial nanospray MXene/ZIF-90@ICG was prepared by incorporating ZIF-90@ICG nanoparticles onto MXene-NH2 nanosheets. MXene/ZIF-90@ICG can on-demand release the antimicrobial factors MXenes, ICG, and Zn2+ in response to variations in pH and ATP levels within the bacterial infection microenvironment. Under NIR radiation, the combination of MXenes, Zn2+, and ICG generated a significant amount of ROS and elevated heat, thereby enhancing the antimicrobial efficacy of PDT and PTT. Meanwhile, NIR excitation could accelerate the further release of ICG and Zn2+, realizing the multimodal synergistic antibacterial effect of PDT/PTT/Zn2+. Notably, introducing MXenes improved the dispersion of the synthesized antimicrobial nanoparticles in aqueous solution, rendering MXene/ZIF-90@ICG a candidate for application as a nanospray. Importantly, MXene/ZIF-90@ICG demonstrated antimicrobial activity and accelerated wound healing in the constructed in vivo subcutaneous Staphylococcus aureus infection model with NIR activation, maintaining a favorable biosafety level. Therefore, MXene/ZIF-90@ICG holds promise as an innovative nanospray for adaptive multimodal synergistic and efficient antibacterial applications with NIR activation.

Dynamic hydrogel–metal–organic framework system promotes bone regeneration in periodontitis through controlled drug delivery

Periodontitis is a prevalent chronic inflammatory disease, which leads to gradual degradation of alveolar bone. The challenges persist in achieving effective alveolar bone repair due to the unique bacterial microenvironment’s impact on immune responses. This study explores a novel approach utilizing Metal–Organic Frameworks (MOFs) (comprising magnesium and gallic acid) for promoting bone regeneration in periodontitis, which focuses on the physiological roles of magnesium ions in bone repair and gallic acid's antioxidant and immunomodulatory properties. However, the dynamic oral environment and irregular periodontal pockets pose challenges for sustained drug delivery. A smart responsive hydrogel system, integrating Carboxymethyl Chitosan (CMCS), Dextran (DEX) and 4-formylphenylboronic acid (4-FPBA) was designed to address this problem. The injectable self-healing hydrogel forms a dual-crosslinked network, incorporating the MOF and rendering its on-demand release sensitive to reactive oxygen species (ROS) levels and pH levels of periodontitis. We seek to analyze the hydrogel’s synergistic effects with MOFs in antibacterial functions, immunomodulation and promotion of bone regeneration in periodontitis. In vivo and in vitro experiment validated the system's efficacy in inhibiting inflammation-related genes and proteins expression to foster periodontal bone regeneration. This dynamic hydrogel system with MOFs, shows promise as a potential therapeutic avenue for addressing the challenges in bone regeneration in periodontitis.Graphical

Seeking Cells, Targeting Bacteria: A Cascade-Targeting Bacteria-Responsive Nanosystem for Combating Intracellular Bacterial Infections.

Intracellular bacteria pose a great challenge to antimicrobial therapy due to various physiological barriers at both cellular and bacterial levels, which impede drug penetration and intracellular targeting, thereby fostering antibiotic resistance and yielding suboptimal treatment outcomes. Herein, a cascade-target bacterial-responsive drug delivery nanosystem, MM@SPE NPs, comprising a macrophage membrane (MM) shell and a core of SPE NPs. SPE NPs consist of phenylboronic acid-grafted dendritic mesoporous silica nanoparticles (SP NPs) encapsulated with epigallocatechin-3-gallate (EGCG), a non-antibiotic antibacterial component, via pH-sensitive boronic ester bonds are introduced. Upon administration, MM@SPE NPs actively home in on infected macrophages due to the homologous targeting properties of the MM shell, which is subsequently disrupted during cellular endocytosis. Within the cellular environment, SPE NPs expose and spontaneously accumulate around intracellular bacteria through their bacteria-targeting phenylboronic acid groups. The acidic bacterial microenvironment further triggers the breakage of boronic ester bonds between SP NPs and EGCG, allowing the bacterial-responsive release of EGCG for localized intracellular antibacterial effects. The efficacy of MM@SPE NPs in precisely eliminating intracellular bacteria is validated in two rat models of intracellular bacterial infections. This cascade-targeting responsive system offers new solutions for treating intracellular bacterial infections while minimizing the risk of drug resistance.

Theranostic antibacterial hydrogel based on biopolymers cross-linked and doped with phytic acid from rice bran for wound healing

Theranostic antibacterial wound dressing is highly recommended in practical applications. The conventional methods of integrating diagnostic and therapeutic functions have the disadvantages of complicated preparation, mutual interference, inability to effectively broad spectrum antibacterial property, and easy to induce drug-resistant bacteria. Herein, a pH and light-responsive theranostic antibacterial hydrogel is developed by biopolymers polyvinyl alcohol (PVA) and polyaniline (PANI), and cross-linking with phytic acid (PA), which is widely present in rice bran. The biological polymer-based conductive hydrogel enables timely diagnosis and photothermal sterilization in-situ for wound healing. Because PANI is highly sensitive to pH changes in the bacterial microenvironment, the hydrogel can detect bacterial infections at concentrations as low as 103 CFU/mL. Subsequently, PANI absorbs near-infrared light to achieve on-demand exothermic sterilization (under 808 nm irradiation for 20 min, the killing ratios for Staphylococcus aureus and Escherichia coli reached almost 100 %). In addition, the hydrogel can monitor the intensity of joint movement to avoid wound re-tearing sensitively. In vitro cytotoxicity and hemocompatibility experiments and in vivo full-thickness infected wound model indicate that the hydrogel has good biocompatibility, antibacterial ability, and can accelerate the wound healing effectively. This work will promote the development of wearable electronic devices and precision medicine.

A long journey to the colon: The role of the small intestine microbiota in intestinal disease.

The small intestine represents a complex and understudied gut niche with significant implications for human health. Indeed, many infectious and non-infectious diseases center within the small intestine and present similar clinical manifestations to large intestinal disease, complicating non-invasive diagnosis and treatment. One major neglected aspect of small intestinal diseases is the feedback relationship with the resident collection of commensal organisms, the gut microbiota. Studies focused on microbiota-host interactions in the small intestine in the context of infectious and non-infectious diseases are required to identify potential therapeutic targets dissimilar from those used for large bowel diseases. While sparsely populated, the small intestine represents a stringent commensal bacterial microenvironment the host relies upon for nutrient acquisition and protection against invading pathogens (colonization resistance). Indeed, recent evidence suggests that disruptions to host-microbiota interactions in the small intestine impact enteric bacterial pathogenesis and susceptibility to non-infectious enteric diseases. In this review, we focus on the microbiota's impact on small intestine function and the pathogenesis of infectious and non-infectious diseases of the gastrointestinal (GI) tract. We also discuss gaps in knowledge on the role of commensal microorganisms in proximal GI tract function during health and disease.

Poly-l-lysine modified MOF nanoparticles with pH/ROS sensitive CIP release and CUR triggered photodynamic therapy against drug-resistant bacterial infection

The challenge of drug resistance in bacteria caused by the over use of biotics is increasing during the therapy process, which has attracted great attentions of the clinicians and scientists around the world. Recently, photodynamic therapy (PDT) triggered by photosensitizer (PS) has become a promising treatment method because of its high efficacy, easy operation, and low side effect. Herein, the poly-l-lysine (PLL) modified metal-organic framework (MOF) nanoparticles, ZIF/PLL-CIP/CUR, were synthesized to allow both reactive oxygen species (ROS) responsive drug release and photodynamic effect for synergistic therapy against drug resistant bacterial infections. The PLL was modified on the shell of the zeolite imidazole framework (ZIF) by the ROS-responsive thioketal linker for controllable CIP release. CUR were encapsulated in ZIF as the photosensitizer for blue light mediated photodynamic effect to produce singlet oxygen (1O2) and superoxide anion radical (O2−) for efficient inhibition towards methicillin-resistant Staphylococcus aureus (MRSA). The charge conversion from negative charge (−4.6 mV) to positive charge (2.6 mV) was observed at pH 7.4 and pH 5.5, and 70.9 % CIP was found released at pH 5.5 in the presence of H2O2, which suggests the good biosafety at physiological pH and ROS-responsive drug release of the as-prepared nanoparticle in the bacterial microenvironment. The as-prepared nanoparticles could effectively kill MRSA and disrupt bacterial biofilm by combination of chemo- and photodynamic therapy. In mice model, the as-prepared nanoparticles exhibited excellent biosafety and synergistic effect with 98.81 % healing rate in treatment of MRSA infection, which is considered as a promising candidate in combating drug resistant bacterial infection.

Quercetin in the Prevention of Induced Periodontal Disease in Animal Models: A Systematic Review and Meta-Analysis.

Periodontitis is an inflammatory condition initiated by oral bacteria and is associated with several systemic diseases. Quercetin is an anti-inflammatory and anti-bacterial poly-phenol present in various foods. The aim of this meta-analysis was the evaluation of the effects of quercetin administration in animal models of experimental periodontitis. A systematic search was performed in electronic databases using the following search terms: "periodontitis" or "periodontal disease" or "gingivitis" and "quercetin" or "cyanidanol" or "sophoretin" or "pentahydroxyflavone". In vivo preclinical animal models of experimental periodontal disease with a measurement of alveolar bone loss were included in the analysis. The risk of bias of the included studies was assessed using the SYRCLE tool. The systematic search yielded 335 results. Five studies were included, four of them qualified for a meta-analysis. The meta-analysis showed that quercetin administration decreased alveolar bone loss (τ2 = 0.31, 1.88 mm 95%CI: 1.09, 2.67) in experimental periodontal disease animal models. However, the risk of bias assessment indicated that four SYRCLE domains had a high risk of bias. Quercetin diminishes periodontal bone loss and prevents disease progression in animal models of experimental periodontal disease. Quercetin might facilitate periodontal tissue hemostasis by reducing senescent cells, decreasing oxidative stress via SIRT1-induced autophagy, limiting inflammation, and fostering an oral bacterial microenvironment of symbiotic microbiota associated with oral health. Future research will show whether and how the promising preclinical results can be translated into the clinical treatment of periodontal disease.

Controllable Assembly of Cu2+ and Chlorin E6 for H2 S-Activatable Recognition of Bacterial Infection and Enhanced Antibacterial Therapy.

Antibacterial photodynamic therapy (APDT) has emerged as one of the intriguing strategies to combat bacterial resistance. However, the antibacterial efficacy of APDT is found to be severely impacted by the hydrogen sulfide (H2 S)-overproduced bacterial infection microenvironment. Herein, a multifunctional APDT platform is developed by assembling Cu2+ and chlorin e6 (Ce6), which exhibits unique H2 S-activatable fluorescence (FL) and antibacterial features. Noteworthily, the assembly conditions are crucial for achievement of Cu-Ce6 nanoassemblies (NAs) with the on-demand responsive properties. The quenched FL and photosensitization of Cu-Ce6 NAs can be selectively activated by the overexpressed H2 S in infected area, enabling specific recognition of bacterial infection and localized antibacterial therapy with minimized side effects. Significantly, amplified oxidative stress is achieved owning to the effective consumption of H2 S by Cu2+ in the NAs, leading to an enhanced APDT. The antibacterial mechanisms including broad-spectrum APDT activity of released Ce6, inherent sterilization effects of produced copper polysulfides and the accompanying disturbance of bacterial sulphide metabolism are further identified. This study may pave a new avenue for the rational design of intelligent APDT platform using minimalist biological building units and thus facilitating the clinical translation of nano-antibacterial agents.

Bacteria-responsive programmed self-activating antibacterial hydrogel to remodel regeneration microenvironment for infected wound healing.

There is still an urgent need to develop hydrogels with intelligent antibacterial ability to achieve on-demand treatment of infected wounds and accelerate wound healing by improving the regeneration microenvironment. We proposed a strategy of hydrogel wound dressing with bacteria-responsive self-activating antibacterial property and multiple nanozyme activities to remodel the regeneration microenvironment in order to significantly promote infected wound healing. Specifically, pH-responsive H2O2 self-supplying composite nanozyme (MSCO) and pH/enzyme-sensitive bacteria-responsive triblock micelles encapsulated with lactate oxidase (PPEL) were prepared and encapsulated in hydrogels composed of L-arginine-modified chitosan (CA) and phenylboronic acid-modified oxidized dextran (ODP) to form a cascade bacteria-responsive self-activating antibacterial composite hydrogel platform. The hydrogels respond to multifactorial changes of the bacterial metabolic microenvironment to achieve on-demand antibacterial and biofilm eradication through transformation of bacterial metabolites, and chemodynamic therapy enhanced by nanozyme activity in conjunction with self-driven nitric oxide (NO) release. The composite hydrogel showed 'self-diagnostic' treatment for changes in the wound microenvironment. Through self-activating antibacterial therapy in the infection stage to self-adaptive oxidative stress relief and angiogenesis in the post-infection stage, it promotes wound closure, accelerates wound collagen deposition and angiogenesis, and completely improves the microenvironment of infected wound regeneration, which provides a new method for the design of intelligent wound dressings.