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1.
Arch Microbiol ; 206(7): 295, 2024 Jun 10.
Article En | MEDLINE | ID: mdl-38856934

Microbial community biofilm exists in the household drinking water system and would pose threat to water quality. This paper explored biofilm formation and chlorination resistance of ten dual-species biofilms in three typical household pipes (stainless steel (SS), polypropylene random (PPR), and copper), and investigated the role of interspecific interaction. Biofilm biomass was lowest in copper pipes and highest in PPR pipes. A synergistic or neutralistic relationship between bacteria was evident in most biofilms formed in SS pipes, whereas four groups displayed a competitive relationship in biofilms formed in copper pipe. Chlorine resistance of biofilms was better in SS pipes and worse in copper pipes. It may be helped by interspecific relationships, but was more dependent on bacteria and resistance mechanisms such as more stable extracellular polymeric substance. The corrosion sites may also protect bacteria from chlorination. The findings provide useful insights for microbial control strategies in household drinking water systems.


Bacteria , Biofilms , Chlorine , Drinking Water , Biofilms/drug effects , Biofilms/growth & development , Chlorine/pharmacology , Bacteria/drug effects , Bacteria/genetics , Bacteria/isolation & purification , Bacteria/classification , Drinking Water/microbiology , Copper/pharmacology , Water Microbiology , Stainless Steel , Polypropylenes , Water Supply , Halogenation , Corrosion , Disinfectants/pharmacology
2.
Appl Microbiol Biotechnol ; 108(1): 357, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38822872

Bacterial plant diseases are difficult to control as the durability of deployed control measures is thwarted by continuous and rapid changing of bacterial populations. Although application of copper compounds to plants is the most widespread and inexpensive control measure, it is often partially efficacious for the frequent appearance of copper-resistant bacterial strains and it is raising concerns for the harmful effects of copper on environment and human health. Consequently, European Community included copper compounds in the list of substances candidates for substitution. Nanotechnologies and the application of nanoparticles seem to respond to the need to find new very effective and durable measures. We believe that Argirium-SUNCs®, silver ultra nanoclusters with an average size of 1.79 nm and characterized by rare oxidative states (Ag2+/3+), represent a valid candidate as a nano-bactericide in the control of plant bacterial diseases. Respect to the many silver nanoparticles described in the literature, Argirium-SUNCs have many strengths due to the reproducibility of the synthesis method, the purity and the stability of the preparation, the very strong (less than 1 ppm) antimicrobial, and anti-biofilm activities. In this mini-review, we provide information on this nanomaterial and on the possible application in agriculture. KEY POINTS: • Argirium-SUNCs have strong antimicrobial activities against phytopathogenic bacteria. • Argirium-SUNCs are a possible plant protection product. • Argirium-SUNCs protect tomato plants against bacterial speck disease.


Metal Nanoparticles , Plant Diseases , Silver , Plant Diseases/microbiology , Plant Diseases/prevention & control , Silver/pharmacology , Metal Nanoparticles/chemistry , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Copper/pharmacology , Biofilms/drug effects , Biofilms/growth & development
3.
ACS Nano ; 18(24): 15845-15863, 2024 Jun 18.
Article En | MEDLINE | ID: mdl-38832685

Nanozyme-driven catalytic therapy provides a promising treatment strategy for bacterial biofilm-infected wounds. However, the single functionality and limited catalytic efficiency of nanozyme-based materials often restrict the effectiveness of wound infection treatment. In this study, CuCo2O4 nanoflowers with multiple enzymatic activities were prepared for antibacterial/antibiofilm treatment by cuproptosis-like death. CuCo2O4 exhibited peroxidase-like (POD-like) and oxidase-like (OXD-like) dual enzyme activities that generated large amounts of •OH and O2•-. Moreover, the glutathione peroxidase-like (GSH-Px-like) activity of CuCo2O4 was able to reduce the overexpression of GSH in the wound microenvironment, enhancing the therapeutic effects of reactive oxygen species (ROS). The morphology of CuCo2O4 was modified using a hydrothermal method with PEG4000 as the solvent, resulting in the exposure of more active center sites and a significant improvement in enzyme catalytic activity. The in vitro results demonstrated the pronounced disruption effect of CuCo2O4 on biofilms formed by bacteria. In vivo, CuCo2O4 significantly promoted angiogenesis, collagen deposition, and cell proliferation. Transcriptome sequencing revealed that elevated ROS levels in bacteria led to cell membrane damage and metabolic disruption. In addition, Cu2+ overload in bacteria induces lipid peroxidation accumulation and disrupts the respiratory chain and tricarboxylic acid (TCA) cycle, ultimately leading to bacterial cuproptosis-like death. This therapeutic strategy, which combines the synergistic effects of multiple enzyme-like activities with cuproptosis-like death, provides an approach for treating biofilm infections.


Anti-Bacterial Agents , Biofilms , Copper , Reactive Oxygen Species , Biofilms/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Reactive Oxygen Species/metabolism , Copper/chemistry , Copper/pharmacology , Animals , Microbial Sensitivity Tests , Staphylococcus aureus/drug effects , Catalysis , Mice
4.
J Colloid Interface Sci ; 671: 751-769, 2024 Oct.
Article En | MEDLINE | ID: mdl-38824748

Chemotherapy and surgery stand as primary cancer treatments, yet the unique traits of the tumor microenvironment hinder their effectiveness. The natural compound epigallocatechin gallate (EGCG) possesses potent anti-tumor and antibacterial traits. However, the tumor's adaptability to chemotherapy due to its acidic pH and elevated glutathione (GSH) levels, coupled with the challenges posed by drug-resistant bacterial infections post-surgery, impede treatment outcomes. To address these challenges, researchers strive to explore innovative treatment strategies, such as multimodal combination therapy. This study successfully synthesized Cu-EGCG, a metal-polyphenol network, and detailly characterized it by using synchrotron radiation and high-resolution mass spectrometry (HRMS). Through chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT), Cu-EGCG showed robust antitumor and antibacterial effects. Cu+ in Cu-EGCG actively participates in a Fenton-like reaction, generating hydroxyl radicals (·OH) upon exposure to hydrogen peroxide (H2O2) and converting to Cu2+. This Cu2+ interacts with GSH, weakening the oxidative stress response of bacteria and tumor cells. Density functional theory (DFT) calculations verified Cu-EGCG's efficient GSH consumption during its reaction with GSH. Additionally, Cu-EGCG exhibited outstanding photothermal conversion when exposed to 808 nm near-infrared (NIR) radiation and produced singlet oxygen (1O2) upon laser irradiation. In both mouse tumor and wound models, Cu-EGCG showcased remarkable antitumor and antibacterial properties.


Anti-Bacterial Agents , Antineoplastic Agents , Catechin , Copper , Nanocomposites , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Copper/chemistry , Copper/pharmacology , Nanocomposites/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Animals , Mice , Humans , Catechin/chemistry , Catechin/pharmacology , Catechin/analogs & derivatives , Microbial Sensitivity Tests , Drug Resistance, Bacterial/drug effects , Photochemotherapy , Wound Infection/drug therapy , Wound Infection/pathology , Wound Infection/microbiology , Drug Screening Assays, Antitumor , Staphylococcus aureus/drug effects , Photothermal Therapy , Particle Size , Escherichia coli/drug effects , Cell Survival/drug effects , Cell Line, Tumor , Surface Properties , Cell Proliferation/drug effects
5.
BMC Microbiol ; 24(1): 213, 2024 Jun 17.
Article En | MEDLINE | ID: mdl-38886632

BACKGROUND: Addressing microbial resistance urgently calls for alternative treatment options. This study investigates the impact of a bimetallic formulation containing colistin, silver, and copper oxide on a pandrug-resistant, highly virulent Pseudomonas aeruginosa (P. aeruginosa) isolate from a cancer patient at the National Cancer Institute, Cairo University, Egypt. METHODS: Silver nanoparticles (Ag NPs), copper oxide nanoparticles (CuO NPs), and bimetallic silver-copper oxide nanoparticles (Ag-CuO NPs) were synthesized using gamma rays, combined with colistin (Col), and characterized by various analytical methods. The antimicrobial activity of Col-Ag NPs, Col-CuO NPs, and bimetallic Col-Ag-CuO NPs against P. aeruginosa was evaluated using the agar well diffusion method, and their minimum inhibitory concentration (MIC) was determined using broth microdilution. Virulence factors such as pyocyanin production, swarming motility, and biofilm formation were assessed before and after treatment with bimetallic Col-Ag-CuO NPs. The in vivo efficacy was evaluated using the Galleria mellonella model, and antibacterial mechanism were examined through membrane leakage assay. RESULTS: The optimal synthesis of Ag NPs occurred at a gamma ray dose of 15.0 kGy, with the highest optical density (OD) of 2.4 at 375 nm. Similarly, CuO NPs had an optimal dose of 15.0 kGy, with an OD of 1.5 at 330 nm. Bimetallic Ag-CuO NPs were most potent at 15.0 kGy, yielding an OD of 1.9 at 425 nm. The MIC of colistin was significantly reduced when combined with nanoparticles: 8 µg/mL for colistin alone, 0.046 µg/mL for Col-Ag NPs, and 0.0117 µg/mL for Col-Ag-CuO NPs. Bimetallic Col-Ag-CuO NPs reduced the MIC four-fold compared to Col-Ag NPs. Increasing the sub-inhibitory concentration of bimetallic nanoparticles from 0.29 × 10-2 to 0.58 × 10-2 µg/mL reduced P. aeruginosa swarming by 32-64% and twitching motility by 34-97%. At these concentrations, pyocyanin production decreased by 39-58%, and biofilm formation was inhibited by 33-48%. The nanoparticles were non-toxic to Galleria mellonella, showing 100% survival by day 3, similar to the saline-treated group. CONCLUSIONS: The synthesis of bimetallic Ag-CuO NPs conjugated with colistin presents a promising alternative treatment for combating the challenging P. aeruginosa pathogen in hospital settings. Further research is needed to explore and elucidate the mechanisms underlying the inhibitory effects of colistin-bimetallic Ag-CuO NPs on microbial persistence and dissemination.


Anti-Bacterial Agents , Biofilms , Colistin , Copper , Metal Nanoparticles , Microbial Sensitivity Tests , Pseudomonas aeruginosa , Silver , Pseudomonas aeruginosa/drug effects , Colistin/pharmacology , Colistin/chemistry , Copper/chemistry , Copper/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Silver/pharmacology , Silver/chemistry , Animals , Metal Nanoparticles/chemistry , Biofilms/drug effects , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Drug Resistance, Multiple, Bacterial/drug effects , Humans , Moths/microbiology , Virulence Factors , Egypt
6.
ACS Appl Mater Interfaces ; 16(23): 29844-29855, 2024 Jun 12.
Article En | MEDLINE | ID: mdl-38829261

Copper plays critical roles as a metal active site cofactor and metalloallosteric signal for enzymes involved in cell proliferation and metabolism, making it an attractive target for cancer therapy. In this study, we investigated the efficacy of polydopamine nanoparticles (PDA NPs), classically applied for metal removal from water, as a therapeutic strategy for depleting intracellular labile copper pools in triple-negative breast cancer models through the metal-chelating groups present on the PDA surface. By using the activity-based sensing probe FCP-1, we could track the PDA-induced labile copper depletion while leaving total copper levels unchanged and link it to the selective MDA-MB-231 cell death. Further mechanistic investigations revealed that PDA NPs increased reactive oxygen species (ROS) levels, potentially through the inactivation of superoxide dismutase 1 (SOD1), a copper-dependent antioxidant enzyme. Additionally, PDA NPs were found to interact with the mitochondrial membrane, resulting in an increase in the mitochondrial membrane potential, which may contribute to enhanced ROS production. We employed an in vivo tumor model to validate the therapeutic efficacy of PDA NPs. Remarkably, in the absence of any additional treatment, the presence of PDA NPs alone led to a significant reduction in tumor volume by a factor of 1.66 after 22 days of tumor growth. Our findings highlight the potential of PDA NPs as a promising therapeutic approach for selectively targeting cancer by modulating copper levels and inducing oxidative stress, leading to tumor growth inhibition as shown in these triple-negative breast cancer models.


Copper , Indoles , Nanoparticles , Polymers , Reactive Oxygen Species , Triple Negative Breast Neoplasms , Copper/chemistry , Copper/pharmacology , Polymers/chemistry , Polymers/pharmacology , Indoles/chemistry , Indoles/pharmacology , Humans , Animals , Mice , Nanoparticles/chemistry , Female , Reactive Oxygen Species/metabolism , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/metabolism , Cell Line, Tumor , Oxidation-Reduction , Nanomedicine , Cell Proliferation/drug effects , Homeostasis/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Superoxide Dismutase-1/metabolism
7.
Nanotechnology ; 35(34)2024 Jun 10.
Article En | MEDLINE | ID: mdl-38788697

Rampant pathogenesis induced by communicable microbes has necessitated development of technologies for rapid and sustained disinfection of surfaces. Copper nanoparticles (CuNPs) have been widely reported for their antimicrobial properties. However, nanostructured copper is prone to oxidative dissolution in the oil phase limiting its sustained use on surfaces and coatings. The current study reports a systematic investigation of a simple synthesis protocol using fatty acid stabilizers (particularly essential oils) for synthesis of copper nanoparticles in the oil phase. Of the various formulations synthesized, rosemary oil stabilized copper nanoparticles (RMO CuNPs) were noted to have the best inactivation kinetics and were also most stable. Upon morphological characterization by TEM and EELS, these were found to be monodispersed (φ5-8 nm) with copper coexisting in all three oxidation states on the surface of the nanoparticles. The nanoparticles were drop cast on woven fabric of around 500 threads per inch and exposed to gram positive bacteria (Staphylococcus aureus), gram negative bacteria (Escherichia coliandPseudomonas aeruginosa), enveloped RNA virus (phi6), non-enveloped RNA virus (MS2) and non-enveloped DNA virus (T4) to encompass the commonly encountered groups of pathogens. It was possible to completely disinfect 107copies of all microorganisms within 40 min of exposure. Further, this formulation was incorporated with polyurethane as thinners and used to coat non-woven fabrics. These also exhibited antimicrobial properties. Sustained disinfection with less than 9% cumulative copper loss for upto 14 washes with soap water was observed while the antioxidant activity was also preserved. Based on the studies conducted, RMO CuNP in oil phase was found to have excellent potential of integration on surface coatings, paints and polymers for rapid and sustained disinfection of microbes on surfaces.


Copper , Metal Nanoparticles , Oils, Volatile , Textiles , Metal Nanoparticles/chemistry , Copper/chemistry , Copper/pharmacology , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Disinfection/methods , Surface Properties , Bacteria/drug effects
8.
Chemosphere ; 360: 142450, 2024 Jul.
Article En | MEDLINE | ID: mdl-38801902

Herein, we successfully synthesized Hf/Zr co-doping on Fe2O3 nanorod photocatalyst by a hydrothermal process and quenching methods. The synergistic roles of Hf and Zr double-doping on the bacteria inactivation test and decomposition of organic pollutants were investigated in detail for the 1 wt% CoOx loaded Hf/Zr-Fe2O3 NRs and CuOx/CoOx loaded Hf/Zr-Fe2O3 NRs photocatalyst. Initially, the rod-like porous morphology of the Hf/Zr-doped Fe2O3 NRs was produced via a hydrothermal method at various Hf co-doping (0, 2, 4, 7 and 10)%. Further, CoOx and CuOx loaded by a wet impregnation approach on the Hf/Zr-Fe2O3 NRs and a highly photoactive Hf(4)/Zr-Fe2O3 [CoOx/CuOx] NRs photocatalyst were developed. After the Hf(4)/Zr-Fe2O3 [CoOx/CuOx] NRs photocatalyst treatment, the Bio-TEM imagery of bacterial cells showed extensive morphological deviations in cell membranes. Hf(4)/Zr-Fe2O3 NR achieved 84.1% orange II degradation upon 3 h illumination, which is higher than that of Hf-Fe2O3 and Zr-Fe2O3 (68.7 and 73.5%, respectively). Additionally, the optimum sample, Hf(4)/Zr-Fe2O3 [CoOx/CuOx] photocatalyst, exhibited 95.5% orange II dye degradation after light radiation for 3 h. Optimized Hf(4)/Zr-Fe2O3 [CoOx/CuOx] catalysts exhibited 99.9% and 99.7% inactivation of E. coli and S. aureus with 120 min, respectively. Further, scavenger experiments revealed that the electrons are the primary responsible species for photocatalytic kinetics. This work will provide a rapid method for the development of high photocatalytic performance materials for bacterial disinfection and organic degradation.


Anti-Bacterial Agents , Copper , Ferric Compounds , Nanotubes , Zirconium , Zirconium/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Catalysis , Nanotubes/chemistry , Ferric Compounds/chemistry , Copper/chemistry , Copper/pharmacology , Hafnium/chemistry , Oxides/chemistry , Cobalt/chemistry , Photochemical Processes
9.
Inorg Chem ; 63(23): 10691-10704, 2024 Jun 10.
Article En | MEDLINE | ID: mdl-38805682

As the main challenge of dental healthcare, oral infectious diseases are highly associated with the colonization of pathogenic microbes. However, current antibacterial treatments in the field of stomatology still lack a facile, safe, and universal approach. Herein, we report the controllable synthesis of copper aluminum-layered double hydroxides (CuAl-LDHs) with high Fenton-like catalytic activity, which can be utilized in the treatment of oral infectious diseases with negligible side effects. Our strategy can efficiently avoid the unwanted doping of other divalent metal ions in the synthesis of Cu-contained LDHs and result in the formation of binary CuAl-LDHs with high crystallinity and purity. Evidenced by experimental and theoretical results, CuAl-LDHs exhibit excellent catalytic ability toward the ·OH generation in the presence of H2O2 and hold strong affinity toward bacteria, endowing them with great catalytic sterilization against both Gram-positive and Gram-negative bacteria. As expected, these CuAl-LDHs provide outstanding treatments for mucosal infection and periodontitis by promoting wound healing and remodeling of the periodontal microenvironment. Moreover, toxicity investigation demonstrates the overall safety. Accordingly, the current study not only provides a convenient and economic strategy for treating oral infectious diseases but also extends the development of novel LDH-based Fenton or Fenton-like antibacterial reagents for further biomedical applications.


Aluminum , Anti-Bacterial Agents , Copper , Hydrogen Peroxide , Copper/chemistry , Copper/pharmacology , Catalysis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/pharmacology , Aluminum/chemistry , Aluminum/pharmacology , Hydroxides/chemistry , Hydroxides/pharmacology , Microbial Sensitivity Tests , Animals , Iron/chemistry , Iron/pharmacology , Oral Health , Mice , Humans , Gram-Negative Bacteria/drug effects
10.
Biomacromolecules ; 25(6): 3345-3359, 2024 Jun 10.
Article En | MEDLINE | ID: mdl-38700942

The management of diabetic ulcers poses a significant challenge worldwide, and persistent hyperglycemia makes patients susceptible to bacterial infections. Unfortunately, the overuse of antibiotics may lead to drug resistance and prolonged infections, contributing to chronic inflammation and hindering the healing process. To address these issues, a photothermal therapy technique was incorporated in the preparation of wound dressings. This innovative solution involved the formulation of a self-healing and injectable hydrogel matrix based on the Schiff base structure formed between the oxidized Bletilla striata polysaccharide (BSP) and hydroxypropyltrimethylammonium chloride chitosan. Furthermore, the introduction of CuO nanoparticles encapsulated in polydopamine imparted excellent photothermal properties to the hydrogel, which promoted the release of berberine (BER) loaded on the nanoparticles and boosted the antibacterial performance. In addition to providing a reliable physical protection to the wound, the developed hydrogel, which integrated the herbal components of BSP and BER, effectively accelerated wound closure via microenvironment regulation, including alleviated inflammatory reaction, stimulated re-epithelialization, and reduced oxidative stress based on the promising results from cell and animal experiments. These impressive outcomes highlighted their clinical potential in safeguarding the wound against bacterial intrusion and managing diabetic ulcers.


Chitosan , Hydrogels , Polysaccharides , Wound Healing , Chitosan/chemistry , Chitosan/analogs & derivatives , Chitosan/pharmacology , Wound Healing/drug effects , Animals , Hydrogels/chemistry , Hydrogels/pharmacology , Polysaccharides/chemistry , Polysaccharides/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Photothermal Therapy/methods , Mice , Humans , Berberine/pharmacology , Berberine/chemistry , Rats , Diabetes Mellitus, Experimental/drug therapy , Copper/chemistry , Copper/pharmacology , Male , Polymers/chemistry , Polymers/pharmacology , Indoles/chemistry , Indoles/pharmacology , Wound Infection/drug therapy , Wound Infection/microbiology , Nanoparticles/chemistry , Staphylococcus aureus/drug effects , Metal Nanoparticles/chemistry
11.
Nano Lett ; 24(20): 6165-6173, 2024 May 22.
Article En | MEDLINE | ID: mdl-38717317

Dynamic therapies, which induce reactive oxygen species (ROS) production in situ through endogenous and exogenous stimulation, are emerging as attractive options for tumor treatment. However, the complexity of the tumor substantially limits the efficacy of individual stimulus-triggered dynamic therapy. Herein, bimetallic copper and ruthenium (Cu@Ru) core-shell nanoparticles are applied for endo-exogenous stimulation-triggered dynamic therapy. The electronic structure of Cu@Ru is regulated through the ligand effects to improve the adsorption level for small molecules, such as water and oxygen. The core-shell heterojunction interface can rapidly separate electron-hole pairs generated by ultrasound and light stimulation, which initiate reactions with adsorbed small molecules, thus enhancing ROS generation. This synergistically complements tumor treatment together with ROS from endogenous stimulation. In vitro and in vivo experiments demonstrate that Cu@Ru nanoparticles can induce tumor cell apoptosis and ferroptosis through generated ROS. This study provides a new paradigm for endo-exogenous stimulation-based synergistic tumor treatment.


Apoptosis , Copper , Reactive Oxygen Species , Ruthenium , Copper/chemistry , Copper/pharmacology , Humans , Reactive Oxygen Species/metabolism , Animals , Ruthenium/chemistry , Ruthenium/pharmacology , Apoptosis/drug effects , Mice , Cell Line, Tumor , Neoplasms/drug therapy , Neoplasms/therapy , Metal Nanoparticles/chemistry , Metal Nanoparticles/therapeutic use , Ligands , Ferroptosis/drug effects , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology
12.
ACS Appl Mater Interfaces ; 16(20): 25856-25868, 2024 May 22.
Article En | MEDLINE | ID: mdl-38726921

Artificial peroxisomes (AP) with enzyme-mimetic catalytic activity and recruitment ability have drawn a great deal of attention in fabricating protocell systems for scavenging reactive oxygen species (ROS), modulating the inflammatory microenvironment, and reprogramming macrophages, which is of great potential in treating inflammatory diseases such as rheumatoid arthritis (RA). Herein, a macrophage membrane-cloaked Cu-coordinated polyphthalocyanine-based AP (CuAP) is prepared with a macrocyclic conjugated polymerized network and embedded Cu-single atomic active center, which mimics the catalytic activity and coordination environment of natural superoxide dismutase and catalase, possesses the inflammatory recruitment ability of macrophages, and performs photoacoustic imaging (PAI)-guided treatment. The results of both in vitro cellular and in vivo animal experiments demonstrated that the CuAP under ultrasound and microbubbles could efficiently scavenge excess ROS in cells and tissues, modulate microenvironmental inflammatory cytokines such as interleukin-1ß, tumor necrosis factor-α, and arginase-1, and reprogram macrophages by polarization of M1 (proinflammatory phenotype) to M2 (anti-inflammatory phenotype). We believe this study offers a proof of concept for engineering multifaceted AP and a promising approach for a PAI-guided treatment platform for RA.


Arthritis, Rheumatoid , Macrophages , Photoacoustic Techniques , Animals , Macrophages/metabolism , Mice , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/therapy , RAW 264.7 Cells , Reactive Oxygen Species/metabolism , Humans , Copper/chemistry , Copper/pharmacology
13.
ACS Nano ; 18(22): 14312-14326, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38767151

Periodontitis, a prevalent chronic inflammatory disease worldwide, is triggered by periodontopathogenic bacteria, resulting in the progressive destruction of periodontal tissue, particularly the alveolar bone. To effectively address periodontitis, this study proposed a nanoformulation known as CuS@MSN-SCS. This formulation involves coating citrate-grafted copper sulfide (CuS) nanoparticles with mesoporous silica (MSNs), followed by surface modification using amino groups and sulfated chitosan (SCS) through electrostatic interactions. The objective of this formulation is to achieve efficient bacteria removal by inducing ROS signaling pathways mediated by Cu2+ ions. Additionally, it aims to promote alveolar bone regeneration through Cu2+-induced pro-angiogenesis and SCS-mediated bone regeneration. As anticipated, by regulating the surface charges, the negatively charged CuS nanoparticles capped with sodium citrate were successfully coated with MSNs, and the subsequent introduction of amine groups using (3-aminopropyl)triethoxysilane was followed by the incorporation of SCS through electrostatic interactions, resulting in the formation of CuS@MSN-SCS. The developed nanoformulation was verified to not only significantly exacerbate the oxidative stress of Fusobacterium nucleatum, thereby suppressing bacteria growth and biofilm formation in vitro, but also effectively alleviate the inflammatory response and promote alveolar bone regeneration without evident biotoxicity in an in vivo rat periodontitis model. These findings contribute to the therapeutic effect on periodontitis. Overall, this study successfully developed a nanoformulation for combating bacteria and facilitating alveolar bone regeneration, demonstrating the promising potential for clinical treatment of periodontitis.


Anti-Bacterial Agents , Bone Regeneration , Chitosan , Copper , Fusobacterium nucleatum , Nanoparticles , Periodontitis , Chitosan/chemistry , Chitosan/pharmacology , Periodontitis/drug therapy , Periodontitis/microbiology , Periodontitis/therapy , Periodontitis/pathology , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Bone Regeneration/drug effects , Rats , Copper/chemistry , Copper/pharmacology , Fusobacterium nucleatum/drug effects , Nanoparticles/chemistry , Rats, Sprague-Dawley , Male , Sulfates/chemistry , Sulfates/pharmacology , Silicon Dioxide/chemistry , Silicon Dioxide/pharmacology , Microbial Sensitivity Tests
14.
Microb Cell Fact ; 23(1): 148, 2024 May 23.
Article En | MEDLINE | ID: mdl-38783243

BACKGROUND: The continuous progress in nanotechnology is rapid and extensive with overwhelming futuristic aspects. Through modernizing inventive synthesis protocols, a paradigm leapfrogging in novelties and findings are channeled toward fostering human health and sustaining the surrounding environment. Owing to the overpricing and jeopardy of physicochemical synthesizing approaches, the quest for ecologically adequate schemes is incontestable. By developing environmentally friendly strategies, mycosynthesis of nanocomposites has been alluring. RESULTS: Herein, a novel architecture of binary CuO and TiO2 in nanocomposites form was fabricated using bionanofactory Candida sp., for the first time. For accentuating the structural properties of CuTi nanocomposites (CuTiNCs), various characterization techniques were employed. UV-Vis spectroscopy detected SPR at 350 nm, and XRD ascertained the crystalline nature of a hybrid system. However, absorption peaks at 8, 4.5, and 0.5 keV confirmed the presence of Cu, Ti and oxygen, respectively, in an undefined assemblage of polygonal-spheres of 15-75 nm aggregated in the fungal matrix of biomolecules as revealed by EDX, SEM and TEM. However, FTIR, ζ-potential and TGA reflected long-term stability (- 27.7 mV) of self-functionalized CuTiNCs. Interestingly, a considerable and significant biocide performance was detected at 50 µg/mL of CuTiNCs against some human and plant pathogens, compared to monometallic counterparts. Further, CuTiNCs (200 µg/mL) ceased significantly the development of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans biofilms by 80.3 ± 1.4, 68.7 ± 3.0 and 55.7 ± 3.0%, respectively. Whereas, 64.63 ± 3.5 and 89.82 ± 4.3% antimicrofouling potentiality was recorded for 100 and 200 µg/ml of CuTiNCs, respectively; highlighting their destructive effect against marine microfoulers cells and decaying of their extracellular polymeric skeleton as visualized by SEM. Moreover, CuTiNCs (100 and 200 µg/ml) exerted significantly outstanding disinfection potency within 2 h by reducing the microbial load (i.e., total plate count, mold & yeast, total coliforms and faecal Streptococcus) in domestic and agricultural effluents reached >50%. CONCLUSION: The synergistic efficiency provided by CuNPs and TiNPs in mycofunctionalized CuTiNCs boosted its recruitment as antiphytopathogenic, antibiofilm, antimicrofouling and disinfectant agent in various realms.


Biofilms , Copper , Nanocomposites , Titanium , Wastewater , Nanocomposites/chemistry , Biofilms/drug effects , Copper/chemistry , Copper/pharmacology , Titanium/chemistry , Titanium/pharmacology , Wastewater/microbiology , Wastewater/chemistry , Candida/drug effects , Disinfection/methods , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Biofouling/prevention & control , Candida albicans/drug effects , Microbial Sensitivity Tests
15.
ACS Nano ; 18(19): 12386-12400, 2024 May 14.
Article En | MEDLINE | ID: mdl-38699808

Current cancer vaccines face challenges due to an immunosuppressive tumor microenvironment and their limited ability to produce an effective immune response. To address the above limitations, we develop a 3-(2-spiroadamantyl)-4-methoxy-4-(3-phosphoryloxy)-phenyl-1,2-dioxetane (alkaline phosphatase substrate) and XMD8-92 (extracellular signal-regulated kinase 5 inhibitor)-codelivered copper-tetrahydroxybenzoquinone (Cu-THBQ/AX) nanosized metal-organic framework to in situ-generate therapeutic vaccination. Once inside the early endosome, the alkaline phosphatase overexpressed in the tumor cells' membrane activates the in situ type I photodynamic effect of Cu-THBQ/AX for generating •O2-, and the Cu-THBQ/AX catalyzes O2 and H2O2 to •O2- and •OH via semiquinone radical catalysis and Fenton-like reactions. This surge of ROS in early endosomes triggers caspase-3-mediated proinflammatory pyroptosis via activating phospholipase C. Meanwhile, Cu-THBQ/AX can also induce the oligomerization of dihydrolipoamide S-acetyltransferase to trigger tumor cell cuproptosis. The production of •OH could also trigger the release of XMD8-92 for effectively inhibiting the efferocytosis of macrophages to convert immunosuppressive apoptosis of cancer cells into proinflammatory secondary necrosis. The simultaneous induction of pyroptosis, cuproptosis, and secondary necrosis effectively converts the tumor microenvironment from "cold" to "hot" conditions, making it an effective antigen pool. This transformation successfully activates the antitumor immune response, inhibiting tumor growth and metastasis.


Cancer Vaccines , Copper , Macrophages , Metal-Organic Frameworks , Pyroptosis , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Animals , Mice , Pyroptosis/drug effects , Macrophages/drug effects , Macrophages/metabolism , Humans , Copper/chemistry , Copper/pharmacology , Cancer Vaccines/chemistry , Tumor Microenvironment/drug effects , Nanoparticles/chemistry , Phagocytosis/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/metabolism , Mice, Inbred BALB C , Efferocytosis , Nanovaccines
16.
Sci Rep ; 14(1): 11354, 2024 05 18.
Article En | MEDLINE | ID: mdl-38762576

According to an estimate, 30% to 40%, of global fruit are wasted, leading to post harvest losses and contributing to economic losses ranging from $10 to $100 billion worldwide. Among, all fruits the discarded portion of oranges is around 20%. A novel and value addition approach to utilize the orange peels is in nanoscience. In the present study, a synthesis approach was conducted to prepare the metallic nanoparticles (copper and silver); by utilizing food waste (Citrus plant peels) as bioactive reductants. In addition, the Citrus sinensis extracts showed the reducing activity against metallic salts copper chloride and silver nitrate to form Cu-NPs (copper nanoparticles) and Ag-NPs (Silver nanoparticles). The in vitro potential of both types of prepared nanoparticles was examined against plant pathogenic bacteria Erwinia carotovora (Pectobacterium carotovorum) and pathogens effect on human health Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Moreover, the in vivo antagonistic potential of both types of prepared nanoparticles was examined by their interaction with against plant (potato slices). Furthermore, additional antipathogenic (antiviral and antifungal) properties were also examined. The statistical analysis was done to explain the level of significance and antipathogenic effectiveness among synthesized Ag-NPs and Cu-NPs. The surface morphology, elemental description and size of particles were analyzed by scanning electron microscopy, transmission electron microscopy, energy-dispersive spectroscopy and zeta sizer (in addition polydispersity index and zeta potential). The justification for the preparation of particles was done by UV-Vis Spectroscopy (excitation peaks at 339 nm for copper and 415 nm for silver) and crystalline nature was observed by X-ray diffraction. Hence, the prepared particles are quite effective against soft rot pathogens in plants and can also be used effectively in some other multifunctional applications such as bioactive sport wear, surgical gowns, bioactive bandages and wrist or knee compression bandages, etc.


Copper , Green Chemistry Technology , Metal Nanoparticles , Pectobacterium carotovorum , Silver , Metal Nanoparticles/chemistry , Silver/chemistry , Silver/pharmacology , Pectobacterium carotovorum/drug effects , Copper/chemistry , Copper/pharmacology , Escherichia coli/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Animals , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Microbial Sensitivity Tests , Humans , Plant Diseases/microbiology , Plant Diseases/prevention & control
17.
J Mater Chem B ; 12(21): 5128-5139, 2024 May 29.
Article En | MEDLINE | ID: mdl-38699827

Optimizing the antibacterial effectiveness of copper ions while reducing environmental and cellular toxicity is essential for public health. A copper chelate, named PAI-Cu, is skillfully created using a specially designed carboxyl copolymer (a combination of acrylic and itaconic acids) with copper ions. PAI-Cu demonstrates a broad-spectrum antibacterial capability both in vitro and in vivo, without causing obvious cytotoxic effects. When compared to free copper ions, PAI-Cu displays markedly enhanced antibacterial potency, being about 35 times more effective against Escherichia coli and 16 times more effective against Staphylococcus aureus. Moreover, Gaussian and ab initio molecular dynamics (AIMD) analyses reveal that Cu+ ions can remain stable in the carboxyl compound's aqueous environment. Thus, the superior antibacterial performance of PAI-Cu largely stems from its modulation of copper ions between mono- and divalent states within the Cu-carboxyl chelates, especially via the carboxyl ligand. This modulation leads to the generation of reactive oxygen species (˙OH), which is pivotal in bacterial eradication. This research offers a cost-effective strategy for amplifying the antibacterial properties of Cu ions, paving new paths for utilizing copper ions in advanced antibacterial applications.


Anti-Bacterial Agents , Chelating Agents , Copper , Escherichia coli , Microbial Sensitivity Tests , Staphylococcus aureus , Copper/chemistry , Copper/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Escherichia coli/drug effects , Chelating Agents/chemistry , Chelating Agents/pharmacology , Staphylococcus aureus/drug effects , Animals , Mice , Reactive Oxygen Species/metabolism , Molecular Structure
18.
Int J Biol Macromol ; 269(Pt 2): 132115, 2024 Jun.
Article En | MEDLINE | ID: mdl-38719015

Bacterial infections pose a serious threat to human health and socioeconomics worldwide. In the post-antibiotic era, the development of novel antimicrobial agents remains a challenge. Polyphenols are natural compounds with a variety of biological activities such as intrinsic antimicrobial activity and antioxidant properties. Metal-polyphenol obtained by chelation of polyphenol ligands with metal ions not only possesses efficient antimicrobial activity but also excellent biocompatibility, which has great potential for application in biomedical and food packaging fields. Herein, we developed metal-polyphenol coordination nanosheets named copper oxidized tannic acid quinone (CuTAQ) possessing efficient antibacterial and anti-biofilm effects, which was synthesized by a facile one-pot method. The synthesis was achieved by chelation of partially oxidized tannic acid (TA) with Cu2+ under mild conditions, which supports low-cost and large-scale production. It was demonstrated that CuTAQ exhibited high antibacterial activity via disrupting the integrity of bacterial cell membranes, inducing oxidative stress, and interfering with metabolism. In addition, CuTAQ exhibits excellent peroxidase catalytic activity and photothermal conversion properties, which play a significant role in enhancing its bactericidal and biofilm scavenging abilities. This study provides insights for rational design of innovative metal-polyphenol nanomaterials with efficient antimicrobial properties.


Anti-Bacterial Agents , Nanostructures , Polyphenols , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Polyphenols/chemistry , Polyphenols/pharmacology , Nanostructures/chemistry , Tannins/chemistry , Tannins/pharmacology , Biofilms/drug effects , Copper/chemistry , Copper/pharmacology , Peroxidase/metabolism , Microbial Sensitivity Tests , Humans
19.
Int J Biol Macromol ; 270(Pt 2): 132029, 2024 Jun.
Article En | MEDLINE | ID: mdl-38704064

Cuproptosis affects osteosarcoma locally, and the exploitation of cuproptosis-related biomaterials for osteosarcoma treatment is still in its infancy. We designed and synthesized a novel injectable gel of Cu ion-coordinated Tremella fuciformis polysaccharide (TFP-Cu) for antiosteosarcoma therapy. This material has antitumor effects, the ability to stimulate immunity and promote bone formation, and a controlled Cu2+ release profile in smart response to tumor microenvironment stimulation. TFP-Cu can selectively inhibit the proliferation of K7M2 tumor cells by arresting the cell cycle and promoting cell apoptosis and cuproptosis. TFP-Cu also promoted the M1 polarization of RAW264.7 cells and regulated the immune microenvironment. These effects increased osteogenic gene and protein expression in MC3T3-E1 cells. TFP-Cu could significantly limit tumor growth in tumor-bearing mice by inducing tumor cell apoptosis and improving the activation of anti-CD8 T cell-mediated immune responses. Therefore, TFP-Cu could be a potential candidate for treating osteosarcoma and bioactive drug carrier for further cancer-related applications.


Apoptosis , Copper , Osteosarcoma , Tumor Microenvironment , Animals , Osteosarcoma/drug therapy , Osteosarcoma/pathology , Mice , Tumor Microenvironment/drug effects , Copper/chemistry , Copper/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Basidiomycota/chemistry , RAW 264.7 Cells , Gels/chemistry , Polysaccharides/pharmacology , Polysaccharides/chemistry , Cell Proliferation/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Bone Neoplasms/drug therapy , Bone Neoplasms/pathology , Fungal Polysaccharides/pharmacology , Fungal Polysaccharides/chemistry
20.
Chemosphere ; 359: 142317, 2024 Jul.
Article En | MEDLINE | ID: mdl-38735492

Titanate nanotubes (TNs) functionalized with CuS nanoparticles using the microwave-assisted hydrothermal method were characterized via XRD, Raman spectroscopy, UV-Vis spectrophotometry, and N2 physisorption. The as-synthesized CuS/TNs had anatase as the main crystalline phase and the band-gap energy was in the visible region, 2.9 eV. The TNs were recrystallized on titania and functionalized with CuS, forming spherical bundles. SEM showed agglomerates of cauliflower-like semispherical particles. The antimicrobial photoactive assets were evaluated against the bacteria Staphylococcus aureus and Escherichia coli. Inhibition was clearly visible in S. aureus after the first 20 min of exposure to a 6-W LED irradiation lamp. The visible-light catalyzed completely and irreversibly the inactivation of S. aureus after 60 min, however, in the case of E. coli, this material only slightly disturbed its growth, which was recovered after 60 min. The successful result obtained with S. aureus can be explained by the fact that it lacks periplasmic superoxide dismutase (SOD) but has staphyloxanthin for external protection against ROS. However, the CuS/TN particles could release Cu2+ ions, which got attached to bacterium structures or entered the cytoplasm; these events together with the generation of ROS under visible LED light helped inactivate quickly staphyloxanthin, thus inflicting permanent damage to the periplasmic membrane.


Copper , Escherichia coli , Light , Staphylococcus aureus , Titanium , Staphylococcus aureus/drug effects , Titanium/chemistry , Titanium/pharmacology , Escherichia coli/drug effects , Copper/chemistry , Copper/pharmacology , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Nanotubes/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry
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