Release Of Copper Ions Research Articles

H2S‐Activated Ion‐Interference Therapy: A Novel Tumor Targeted Therapy Based on Copper‐Overload‐Mediated Cuproptosis and Pyroptosis

AbstractCopper overload is a novel way to achieve copper‐ion‐interference therapy by disrupting copper homeostasis and treating diseases through multiple cell death pathways. However, it is difficult to reach copper overload since excess intracellular copper ions will be pumped out. Herein, copper overload is achieved by both raising cellular uptake and reducing the efflux of copper ions using hydrogen sulfide (H2S)‐responsive copper hydroxyphosphate nanoparticles (Cu2(PO4)(OH) NPs). After immersion in an H2S‐enriched colon cancer microenvironment, Cu2(PO4)(OH) NPs can transform into copper sulfide NPs with reduced size for higher cell entering, resulting in improved Fenton activity as well as copper ion dissociation. Reactive oxygen species generated by the Fenton reaction not only activate inflammasomes and Caspase‐1 proteins, cause the cleavage of gasdermin D to induce pyroptosis, but also affect mitochondrial function and down‐regulate copper exporter ATP7A to further reduce the copper excretion. The combination of higher endocytosis and lower exportation leads to maximized copper overload. Together with the efficient copper ions release, mitochondrial tricarboxylic acid cycle can be disrupted and iron‐sulfur cluster proteins are downregulated, ultimately triggering cuproptosis. As both pyroptosis and cuproptosis are efficient ways to induce cell death, this study provides a novel way to realize effective tumor‐targeted therapy based on H2S‐activated copper overload with simple Cu2(PO4)(OH) NPs.

3D printed hollow channeled hydrogel scaffolds with antibacterial and wound healing activities

The development of hydrogel based scaffold with the capability of enhanced antibacterial effects and wound healing is the promising strategy for the treatment of wound tissues with bacterial infection. Herein, we fabricated a hollow channeled hydrogel scaffold based on the mixture of dopamine modified alginate (Alg-DA) and gelatin via co-axial 3D printing for the treatment of bacterial-infected wound. The scaffold was crosslinked by copper/calcium ions, which could enhance the structural stability and mechanical properties. Meanwhile, copper ions crosslinking endowed the scaffold with good photothermal effects. The photothermal effect and copper ions showed excellent antibacterial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. Moreover, the hollow channels and the sustained released copper ions could stimulate angiogenesis and accelerate wound healing process. Thus, the prepared hollow channeled hydrogel scaffold might be a potential candidate for promoting wound healing application.

Type-I AIE Photosensitizer Loaded Biomimetic System Boosting Cuproptosis to Inhibit Breast Cancer Metastasis and Rechallenge.

Cuproptosis shows good application prospects in tumor therapy. However, the copper efflux mechanism and highly expressed intracellular reducing substances can inhibit the cuproptosis effects. In this study, a platelet vesicle (PV) coated cuprous oxide nanoparticle (Cu2O)/TBP-2 cuproptosis sensitization system (PTC) was constructed for multiple induction of tumor cuproptosis. PTC was prepared by physical extrusion of AIE photosensitizer (TBP-2), Cu2O, and PV. After the biomimetic modification, PTC can enhance its long-term blood circulation and tumor targeting ability. Subsequently, PTC was rapidly degraded to release copper ions under acid conditions and hydrogen peroxides in tumor cells. Then, under light irradiation, TBP-2 quickly enters the cell membrane and generates hydroxyl radicals to consume glutathione and inhibit copper efflux. Accumulated copper can cause lipoylated protein aggregation and iron-sulfur protein loss, which result in proteotoxic stress and ultimately cuproptosis. PTC treatment can target and induce cuproptosis in tumor cells in vitro and in vivo, significantly inhibit lung metastasis of breast cancer, increase the number of central memory T cells in peripheral blood, and prevent tumor rechallenge. It provides an idea for the design of nanomedicine based on cuproptosis.

Injectable thermo-sensitive hydrogel loaded hollow copper sulfide nanoparticles for ROS burst in TME and effective tumor treatment.

Introduction: Lung cancer the most prevalent cause of cancer-related deaths, and current therapies lack sufficient specificity and efficacy. This study developed an injectable thermosensitive hydrogel harboring hollow copper sulfide nanoparticles and β-lapachone (Lap) (CLH) for lung tumor treatment. Methods: The hydrogel-encapsulated CLH system can remotely control the release of copper ions (Cu2+) and drugs using photothermal effects for non-invasive controlled-release drug delivery in tumor therapy. The released Cu2+ consumes the overexpressed GSH in TME and the generated Cu+ further exploits the TME characteristics to initiate nanocatalytic reactions for generating highly toxic hydroxyl radicals. In addition, in cancer cells overexpressing Nicotinamide adenine dinucleotide (phosphate): quinone oxidoreductase 1 (NQO1), Lap can catalyze the generation of hydrogen peroxide (H2O2) through futile redox cycles. H2O2 is further converted into highly toxic hydroxyl radicals via the Fenton-like reaction, leading to a burst of reactive oxygen species in TME, which further enhances the therapeutic effect of chemokines. Results: Analysis of the antitumor efficacy in a subcutaneous A549 lung tumor model mice showed a significant delay in tumor growth and no systemic toxicity was detected. Discussion: In conclusion, we have established a CLH nanodrug platform that enables efficient lung tumor therapy through combined photothermal/chemodynamic therapy (CDT) treatment and self-supplying H2O2 to achieve cascade catalysis, leading to explosive amplification of oxidative stress.

Temperature-Responsive Nanoassemblies for Self-Regulated Photothermal Therapy and Controlled Copper Release to Accelerate Chronic Wound Healing.

Photothermal therapy (PTT) is an effective therapeutic method against multidrug-resistant bacteria. The heating temperature is of great significance to completely eliminate bacteria but not damage surrounding healthy tissue. To meet the need for chronic wound management, a pH and temperature dual-responsive copper-gold nanoassembly (sCuAu NAs) was constructed by cross-linking the CuAu nanoparticles (CuAu NPs) with small molecules involved in the Edman degradation reaction. At room temperature, the sCuAu NAs could quickly heat up to eliminate the biofilm upon laser irradiation due to the surface plasmon resonance coupling effect. On arriving at the degradation temperature of around 50 °C, the sCuAu NAs are disassembled into CuAu NPs in the wound infection site, which not only prevents overheating but also promotes deep penetration and accelerates copper-ion release to remove residual bacteria and promote wound healing. This study not only provides an effective treatment that can simultaneously alleviate wound infection and accelerate wound healing but also brings up an idea on the development and application of temperature self-regulated photothermal agents in various diseases.

CuCeO Bimetallic Oxide Rapidly Treats Staphylococcus aureus-Infected Osteomyelitis through Microwave Strengthened Microwave Catalysis and Fenton-Therapy.

Osteomyelitis caused by bacteria is a deep-seated lesion and is often treated clinically with antibiotics. Long-term use of antibiotics may predispose bacteria to develop resistance. Here, CuCeOx material is applied to treat infectious bacterial osteomyelitis using microwave (MW)-assisted bacterial killing. Heat generation occurs as a result of the dielectric properties of the material under MW irradiation, and the material generates reactive oxygen species (ROS) under MW irradiation. Heat and ROS increase the thermal sensitivity and permeability of bacterial cell membranes, and the released copper ions easily penetrate the bacterial membrane and react with H2 O2 to produce a toxic hydroxyl group inside the bacteria, leading to the bacteria's eventual death. This is due to the synergistic effect of the MW thermal effect, ROS, and the breaking of the equilibrium within the bacteria. CuCeOx can effectively treat osteomyelitis caused by Staphylococcus aureususing MW irradiation. This study can safely and effectively address the challenge of deep tissue infections by shedding light on non-invasive antimicrobial systems and using MW thermal therapy and MW dynamics to achieve therapeutic results.

Adhesive Composite Microspheres with Dual Antibacterial Strategies for Infected Wound Healing.

Skin damage and infection pose a severe challenge to human health. Construction of a novel versatile dressing with good anti-infection and healing-promoting abilities is greatly expected. In this paper, nature-source-based composite microspheres with dual antibacterial mechanisms and bioadhesive features by microfluidics electrospray for infected wound healing is developed. The microspheres enable sustained release of copper ions, which not only show long-term antibacterial properties, but also play important role in wound-healing-related angiogenesis. Additionally, the microspheres are coated with polydopamine via self-polymerization, which renders the microspheres adhesive to the wound surface, and further enhance the antibacterial ability through photothermal energy conversion. Based on the dual antibacterial strategies provided by copper ions and polydopamine as well as the bioadhesive property, the composite microspheres exhibit excellent anti-infection and wound healing performances in a rat wound model. These results, along with the nature-source-based composition and biocompatibility, indicate the great potential of the microspheres in clinical wound repair.

Corrosion of copper nickel titanium archwire in chlorhexidine, sodium fluoride, and chitosan mouthwashes.

Copper (Cu), nickel (Ni), chromium (Cr) ion release, and surface topography change from the orthodontic wire are the initial processes of corrosion that may affect the mechanical properties of the archwire. In this study, we aim to evaluate the effect of CHX, NaF, and chitosan on the corrosion of CuNiTi wire nickel and copper ions released, surface roughness change, and archwire deflection. Ninety samples of CuNiTi Tanzo™ archwires were divided into five groups according to their immersion solution: Artificial Saliva, CHX, NaF, CHX-NaF, and chitosan group. Each group was further divided into three subgroups (n=6) corresponding immersion time, i.e., two, four, and six weeks. The corrosion of the samples was analyzed with an atomic absorption spectrophotometer (AAS), scanning electron microscope (SEM), and universal testing machine (UTM). The amount of nickel ion releases was increasing, but the copper ion releases were reduced by the time of observations. The highest nickel ion was released in the CHX-NaF group and the lowest in the chitosan group for six-week immersion. It also corresponded to the surface topography by SEM analysis which showed the most extended cracks and deep pits in the CHX-NaF group and a smoother surface in the chitosan group. Copper ion release showed the highest ion release in the NaF group and the lowest release in the chitosan group. The unloading force of CuNiTi archwire deflection remains the same at week two and week four for all mouthwashes. The use of mouthwashes that contained CHX, NaF, and chitosan could further alter the passive layer and cause higher nickel and copper ion release and increased CuNiTi archwire surface structure porosity. But there is no distinction between mouthwashes to release the unloading force within two until four weeks.

In Situ Microscopic Studies on the Interaction of Multi-Principal Element Nanoparticles and Bacteria.

Multi-principal element nanoparticles are an emerging class of materials with potential applications in medicine and biology. However, it is not known how such nanoparticles interact with bacteria at nanoscale. In the present work, we evaluated the interaction of multi-principal elemental alloy (FeNiCu) nanoparticles with Escherichia coli (E. coli) bacteria using the in situ graphene liquid cell (GLC) scanning transmission electron microscopy (STEM) approach. The imaging revealed the details of bacteria wall damage in the vicinity of nanoparticles. The chemical mappings of S, P, O, N, C, and Cl elements confirmed the cytoplasmic leakage of the bacteria. Our results show that there is selective release of metal ions from the nanoparticles. The release of copper ions was much higher than that for nickel while the iron release was the lowest. In addition, the binding affinity of bacterial cell membrane protein functional groups with Cu, Ni, and Fe cations is found to be the driving force behind the selective metal cations' release from the multi-principal element nanoparticles. The protein functional groups driven dissolution of multielement nanoparticles was evaluated using the density functional theory (DFT) computational method, which confirmed that the energy required to remove Cu atoms from the nanoparticle surface was the least in comparison with those for Ni and Fe atoms. The DFT results support the experimental data, indicating that the energy to dissolve metal atoms exposed to oxidation and/or the to presence of oxygen atoms at the surface of the nanoparticle catalyzes metal removal from the multielement nanoparticle. The study shows the potential of compositional design of multi-principal element nanoparticles for the controlled release of metal ions to develop antibacterial strategies. In addition, GLC-STEM is a promising approach for understanding the nanoscale interaction of metallic nanoparticles with biological structures.

Multifunctional Three-Dimensional Printed Copper Loaded Calcium Phosphate Scaffolds for Bone Regeneration

Bone regeneration using inorganic nanoparticles is a robust and safe approach. In this paper, copper nanoparticles (Cu NPs) loaded with calcium phosphate scaffolds were studied for their bone regeneration potential in vitro. The pneumatic extrusion method of 3D printing was employed to prepare calcium phosphate cement (CPC) and copper loaded CPC scaffolds with varying wt% of copper nanoparticles. A new aliphatic compound Kollisolv MCT 70 was used to ensure the uniform mixing of copper nanoparticles with CPC matrix. The printed scaffolds were studied for physico-chemical characterization for surface morphology, pore size, wettability, XRD, and FTIR. The copper ion release was studied in phosphate buffer saline at pH 7.4. The in vitro cell culture studies for the scaffolds were performed using human mesenchymal stem cells (hMSCs). The cell proliferation study in CPC-Cu scaffolds showed significant cell growth compared to CPC. The CPC-Cu scaffolds showed improved alkaline phosphatase activity and angiogenic potential compared to CPC. The CPC-Cu scaffolds showed significant concentration dependent antibacterial activity in Staphylococcus aureus. Overall, the CPC scaffolds loaded with 1 wt% Cu NPs showed improved activity compared to other CPC-Cu and CPC scaffolds. The results showed that copper has improved the osteogenic, angiogenic and antibacterial properties of CPC scaffolds, facilitating better bone regeneration in vitro.

Acid-degradable nanocomposite hydrogel and glucose oxidase combination for killing bacterial with photothermal augmented chemodynamic therapy

Bacterial infection often delays diabetic wound healing, and even causes serious life-threatening complications. Herein, we successfully developed a Cu2O/Pt nanocubes-dopping alginate (ALG)- hyaluronic acid (HA) hydrogel (Cu2O/Pt hydrogel) by simple assembly of the Cu2O/Pt nanocubes and the ALG-HA mixture. The Cu2O/Pt hydrogel combined with the glucose oxidase (GOx) can be used for photothermal- and starving-enhanced chemodynamic therapy (CDT) against Gram-negative and Gram-positive bacteria. The GOx can catalyze the glucose to produce gluconic acid and H2O2 for starvation therapy, following which the released Cu2O/Pt nanocubes react with H2O2 in the acidic microenvironment to generate highly cytotoxic hydroxyl radicals (·OH) for CDT. Additionally, the Cu2O/Pt hydrogel can release copper ions gradually with the decrease of pH induced by gluconic acid, which can increase the protein expression and secretion of vascular endothelial growth factor (VEGF) and promote endothelial cell proliferation, migration and angiogenesis, subsequently promoting diabetic wound healing in rats. Our results suggested that the Cu2O/Pt hydrogel combined with GOx may be a potential therapeutic approach for treating the infected diabetic wound.

Corrosion of copper nickel titanium archwire in chlorhexidine, sodium fluoride, and chitosan mouthwashes

Background: Copper (Cu), nickel (Ni), chromium (Cr) ion release, and surface topography change from the orthodontic wire are the initial processes of corrosion that may affect the mechanical properties of the archwire. In this study, we aim to evaluate the effect of CHX, NaF, and chitosan on the corrosion of CuNiTi wire nickel and copper ions released, surface roughness change, and archwire deflection. Methods: Ninety samples of CuNiTi Tanzo™ archwires were divided into five groups according to their immersion solution: Artificial Saliva, CHX, NaF, CHX-NaF, and chitosan group. Each group was further divided into three subgroups (n=6) corresponding immersion time, i.e., two, four, and six weeks. The corrosion of the samples was analyzed with an atomic absorption spectrophotometer (AAS), scanning electron microscope (SEM), and universal testing machine (UTM). Results: The amount of nickel ion releases was increasing, but the copper ion releases were reduced by the time of observations. The highest nickel ion was released in the CHX-NaF group and the lowest in the chitosan group for six-week immersion. It also corresponded to the surface topography by SEM analysis which showed the most extended cracks and deep pits in the CHX-NaF group and a smoother surface in the chitosan group. Copper ion release showed the highest ion release in the NaF group and the lowest release in the chitosan group. The unloading force of CuNiTi archwire deflection remains the same at week two and week four for all mouthwashes. Conclusion: The use of mouthwashes that contained CHX, NaF, and chitosan could further alter the passive layer and cause higher nickel and copper ion release and increased CuNiTi archwire surface structure porosity. But there is no distinction between mouthwashes to release the unloading force within two until four weeks.

Formation of a novel Cu-containing bioactive glass nano-topography coating with strong bactericidal capability and bone regeneration

Implant-related infection (IRI) is a disastrous complication after total joint arthroplasty (TJA). Due to its cytocompatibility and mechanically resistance, titanium (Ti) has been recognized as suitable bone implant materials. However, Ti lacks bioactivity and is vulnerable to bacterial infection. In this study, we developed an innovative surface coating using electrophoretic deposition (EPD) to overcome those limitations. The coating was composed of (i) a natural biocompatibility polymer Chitosan (Chit), and (ii) a novel copper-doped bioactive glass nanoparticles (Cu-BGNs) with antibacterial and pro-osteogenic properties. In vitro experiments showed that this coating endowed the Ti surface with the ability to promote macrophage M1 polarization through topography cues and released copper ions. The coating combining immunoregulatory antibacterial effects with transient bactericidal activity led to synergetic effects against IRIs. Furthermore, the coated Ti implants exerted favorable osteo-immunomodulatory effects towards enhanced osteogenic abilities as evidenced in vitro and in vivo. This strategy combining Cu-BGNs-Chit composites and EPD provides novel strategies for designing and fabricating immunomodulatory implants targeting IRIs.

Chitosan’s effects on the acidity, copper ion release, deflection, and surface roughness of copper-nickel-titanium archwire

Background: Chitosan has an antimicrobial effect in oral hygiene control. Orthodontists sometimes prescribe mouthwash to adolescent patients. Copper-nickel-titanium (CuNiTi) orthodontic archwire is widely used in orthodontic treatment. Chitosan’s effects on the CuNiTi properties of orthodontic archwire are not generally known. Purpose: This study aimed to measure the acidity, copper ion release, deflection, and surface roughness of CuNiTi orthodontic archwire immersed in artificial saliva and 2% chitosan. Methods: This study comprised experimental laboratory research. Forty-two CuNiTi orthodontic archwires were divided into three groups. Group A consisted of 18 archwires immersed in artificial saliva, Group B consisted of 18 archwires immersed in 2% chitosan, and Group C was six archwires for the baseline sample. The two intervention groups (A and B) were divided into three subgroups of six samples and were subjected to different immersion times—i.e., two, four, and six weeks. Acidity, copper ion release, deflection, and surface roughness were measured using pH meters, atomic absorption spectrophotometry (AAS), a universal testing machine (UTM), and a scanning electron microscope (SEM). Results: The results showed that Group A was more alkaline than Group B, and it was significantly different only in Week 2. Group B’s copper ion release was significantly lower than Group A for all the time observations (p<0.05), and the deflection analysis showed no significant difference in any of the groups (p>0.05). Furthermore, the SEM images showed CuNiTi in Group A at Week-6 had the most porosities and defects. Conclusion: The chitosan produces buffer effects on the pH; it also exhibits lower copper ion release, no differences in unloading forces, and subjectively has better surface roughness.

Nickel and copper ion release, deflection and the surface roughness of copper-nickel-titanium orthodontic archwire in sodium fluoride solution.

Sodium fluoride (NaF) is commonly used in oral hygiene products, leading to corrosion and reduced archwire properties. In addition, ion release can cause allergies and become toxic to the oral environment. This research aimed to observe the Nickel (Ni) and Copper (Cu) ions released that affected initial corrosion as deflection and surface roughness changed in the Copper-Nickel-Titanium (CuNiTi) archwire. The total samples were 54 copper-nickel-titanium (CuNiTi-Tanzo, American orthodontic®) archwires immersed in three solutions. Artificial saliva was used in the control group NaF 0.05%, and a NaF 0.15% solution was used in the intervention groups (n = 6). The groups were divided into three observation times (two, four, and six weeks). Cu and Ni ions released, deflection, the surface roughness of the archwires, and solution acidities were recorded and analyzed. Ni and Cu ion release and surface roughness of the CuNiTi archwires significantly increased as the NaF concentration increased. The Ni ion release improved along the immersion period; the opposite was true for the Cu ion release. The solutions became more alkaline after the CuNiTi archwires were immersed. The pH and the archwires' deflections of the three solutions did not show significant differences. The NaF increased Cu-Ni ion release and surface roughness but not the deflection force of the CuNiTi. The increase was affected by the concentration and duration of immersion.

Silk fibroin/chitosan coating with tunable catalytic nitric oxide generation for surface functionalization of cardiovascular stents

Developing a functional coating for vascular stents with sustainable and tunable NO release remains challenging. In this work, we report a silk fibroin/chitosan-based biopolymer coating incorporating copper ions as a catalyst for NO generation and demonstrate its potential for the surface functionalization of cardiovascular stents. Based on the differences in silk fibroin and chitosan coordinating with copper ions, the loading, bonding, and release of copper ions could be precisely regulated over a wide range by controlling the ratio of silk fibroin and chitosan. This system shows good cytocompatibility for endothelial cells and tunable catalytic activity to decompose S-nitroso-N-acetyl-D-penicillamine (SNAP) for NO generation. Consequently, a functionalized coating with sustainable and tunable NO catalysis generation was developed on the metallic stent. Based on good biocompatibility, tunable NO release, and simple processing, the coating is expected to have great promise in the field of intervention therapy of cardiovascular disease.

The co-occurrent microplastics and nano-CuO showed antagonistic inhibitory effects on bacterial denitrification: Interaction of pollutants and regulations on functional genes

The wide occurrence of microplastics (MPs) and nanoparticles resulted in their inevitable coexistence in environment. However, the joint effects of these two types of particulate emerging contaminants on denitrification have seldomly been investigated. Herein, non-biodegradable polyvinyl chloride, polypropylene, polyethylene and biodegradable polyhydroxyalkanoate (PHA) MPs were chosen to perform the co-occurrent effects with nano copper oxide (nano-CuO). Both the nano-CuO and MPs inhibited the denitrification process, and biodegradable PHA-MPs showed severer inhibition than non-biodegradable MPs. However, the presence of MPs significantly alleviated the inhibition of nano-CuO, suggesting an antagonistic effect. Other than MPs decreasing copper ion release from nano-CuO, MPs and nano-CuO formed agglomerations and induced lower levels of oxidative stress compared to individual exposure. Transcriptome analysis indicated that the co-occurrent MPs and nano-CuO induced different regulation on denitrifying genes (e. g. nar and nor) compared to individual ones. Also, the expressions of genes involved in denitrification-associated metabolic pathways, including glycolysis and NADH electron transfer, were down-regulated by nano-CuO or MPs, but exhibiting recovery under the co-occurrent conditions. This study firstly discloses the antagonistic effect of nano-CuO and MPs on environmental process, and these findings will benefit the systematic evaluation of MPs environmental behavior and co-occurrent risk with other pollutants.

Catalytic immunotherapy-photothermal therapy combination for melanoma by ferroptosis-activating vaccine based on artificial nanoenzyme

Tumor cell vaccine is a promising approach for cancer therapy to activate tumor immune, which can be achieved by tumor cells immunogenic cell death (ICD), converting in situ tumors into endogenous vaccination strategy, and ferroptosis has been proved to induce ICD occurrence. Ferroptosis is triggered by artificial nanoenzyme copper telluride mimicking peroxidase and glutathione oxidase, based on which the ferroptosis-activating vaccine (termed as CM CTNPs@OVA) was designed and established for catalytic immunotherapy. Owing to photothermal effect of copper telluride, photothermal therapy (PTT) was combined for an intensive cancer therapeutic effect. CM CTNPs@OVA was composed of solid mesoporous copper telluride nanoparticles, ovalbumin (OVA) loaded in mesoporous, and melanoma cell membrane coating surface. In in vitro and in vivo investigations, CM CTNPs@OVA, with particle size of 113.7 ± 1.7 nm, was certified to release copper ions for ferroptosis initiation, and OVA directly maturated dendritic cell (DC) as exogenous antigens extracellularly. ICD was then induced by ferroptosis pathway and PTT to release damage-associated molecular patterns for DC maturation and subsequent T cells recruitment. CM CTNPs@OVA-treated melanoma with exited inhibition rate, proving that the strategy of catalytic immunotherapy-PTT combination by ferroptosis-activating vaccine possessed massive potential for melanoma therapy based on nanoenzyme copper telluride.

Enhanced decomplexation of Cu-EDTA and simultaneous removal of Cu(II) by electron beam irradiation accompanied with autocatalytic fenton-like reaction: Synergistic performance and mechanism

Widely existing heavy metal complexes with high stability and poor biodegradability are intractable to be eliminated by conventional methods. In this study, electron beam (EB) irradiation characterized by rapidly producing strong oxidizing radicals was employed to effectively decompose Cu-ethylenediaminetetraacetic acid (Cu-EDTA) with almost complete elimination at 5 kGy. In terms of heavy metal removal, EB irradiation at relatively low doses was insufficient to remove copper ions, which was only 17.2% under 15 kGy. However, with the extra addition of 8 mM H2O2, such an irradiation dose could result in 99.0% copper ions removal. Mechanism analysis indicated that EB irradiation combined with spontaneously induced Fenton-like reactions were responsible for its excellent performance. The prime function of EB irradiation was to destroy the structure of Cu-EDTA with in-situ produced ·OH, and the subsequent released Cu-based intermediates could activate H2O2 to initiate autocatalytic chain reactions, correspondingly accelerating the degradation of complexes and the liberation of metal ions. Highly oxidative ·OH and O2·− were demonstrated as main active species acted on different positions of Cu-EDTA to realize gradual decarboxylation, synchronously generating low molecular weight compounds. XRD and XPS analysis showed that the released copper ions were mainly precipitated in the form of CuO, Cu(OH)2 and Cu2(OH)2CO3. In general, EB/H2O2 was an adoptable strategy for the disposal of such refractory heavy metal complexes.

Copper-rich multifunctional Prussian blue nanozymes for infected wound healing

The healing process of infected wounds was limited by bacterial infection, excessive reactive oxygen species (ROS) accumulation, and tissue hypoxia. In order to alleviate the above situations, herein, a copper-rich multifunctional ultra-small Prussian blue nanozymes (HPP@Cu NZs) was constructed for infected wound synergistic treatment. Firstly, hyaluronic acid was modified by branched polyethyleneimine which could form a complex with copper ions, to construct copper-rich Prussian blue nanozymes. Secondly, the HPP@Cu NZs have a uniform ultra-small nano size and excellent photothermal response performance, exhibition of multifunctional enzymatic activity and anti-inflammatory properties. Finally, the slow release of copper ions in the HPP@Cu NZs could effectively promote the formation of new blood vessels, thus giving it multifunctional properties. In vitro and in vivo experiments showed that it not only could effectively inhibit and kill bacteria under 808 nm near-infrared laser but also could remove excessive ROS, regulate oxygen levels, and anti-inflammation. More importantly, the release of copper ions could synergistically promote the healing of infected wounds as well as good biocompatibility. Overall, our studies provide a multifunctional strategy for infected wounds with synergistic treatment based on carrier construction.