Glutathione Peroxidase-like Activity Research Articles

CuCo2O4 Nanoflowers with Multiple Enzyme Activities for Treating Bacterium-Infected Wounds via Cuproptosis-like Death.

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.

Photothermal/photodynamic synergistic antibacterial study of MOF nanoplatform with SnFe2O4 as the core

Drug-resistant bacterial infections cause significant harm to public life, health, and property. Biofilm is characterized by overexpression of glutathione (GSH), hypoxia, and slight acidity, which is one of the main factors for the formation of bacterial resistance. Traditional antibiotic therapy gradually loses its efficacy against multi-drug-resistant (MDR) bacteria. Therefore, synergistic therapy, which regulates the biofilm microenvironment, is a promising strategy. A multifunctional nanoplatform, SnFe2O4-PBA/Ce6@ZIF-8 (SBC@ZIF-8), in which tin ferrite (SnFe2O4, denoted as SFO) as the core, loaded with 3-aminobenzeneboronic acid (PBA) and dihydroporphyrin e6 (Ce6), and finally coated with zeolite imidazole salt skeleton 8 (ZIF-8). The platform has a synergistic photothermal therapy (PTT)/photodynamic therapy (PDT) effect, which can effectively remove overexpressed GSH by glutathione peroxidase-like activity, reduce the antioxidant capacity of biofilm, and enhance PDT. The platform had excellent photothermal performance (photothermal conversion efficiency was 55.7 %) and photothermal stability. The inhibition rate of two MDR bacteria was more than 96 %, and the biofilm clearance rate was more than 90 % (150 μg/mL). In the animal model of MDR S. aureus infected wound, after 100 μL SBC@ZIF-8+NIR (150 μg/mL) treatment, the wound area of mice was reduced by 95 % and nearly healed. The serum biochemical indexes and H&E staining results were within the normal range, indicating that the platform could promote wound healing and had good biosafety. In this study, we designed and synthesized multifunctional nanoplatforms with good anti-drug-resistant bacteria effect and elucidated the molecular mechanism of its anti-drug-resistant bacteria. It lays a foundation for clinical application in treating wound infection and promoting wound healing.

A multipronged strategy for encephalitis: Oxidative stress reduction and inflammatory microenvironment modulation by a neuroprotective selenium-based nanomedicine

The elevated levels of reactive oxygen species (ROS) in the inflammatory microenvironment associated with encephalitis, trigger neurological damage and immune imbalance. Owing to the complex environment of the brain, there are few effective therapies for the treatment of encephalitis. Accordingly, the development of multifunctional drugs to alleviate encephalitis under this complex microenvironment is urgently needed. In this study, multifunctional metal-polyphenol-coated selenium nanoparticles (BSe@MT) were synthesized by combining albumin-dispersed selenium nanoparticles (BSe) and a metal-polyphenol complex based on manganese ions and tannic acid. BSe@MT exhibited superoxide dismutase-like and glutathione peroxidase-like activities, which enabled scavenging of the excess intracellular ROS, thus effectively inhibiting neuronal apoptosis and alleviating microglia inflammatory responses in vitro. Furthermore, the nanoparticles exhibited good in vivo therapeutic effects in a mouse model of encephalitis by effectively decreasing the ROS levels, lipid peroxidation, and neuronal loss. In addition, BSe@MT modulated the inflammatory microenvironment associated with encephalitis by inhibiting microglia polarization and neutrophil infiltration, downregulating the levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), and upregulating the levels of anti-inflammatory cytokines (IL-10). Further examination of the mechanism revealed that BSe@MT significantly downregulated the expression of inflammatory-response-related genes such as Map3k8, Socs3, and Cxcl10, thereby alleviating the inflammatory response. Moreover, BSe@MT displayed good biocompatibility and was primarily metabolized by the liver and kidneys. Overall, BSe@MT is expected to provide a safe, effective, and multipronged strategy for the treatment of encephalitis by rebalancing the complex microenvironment.

Zeolitic imidazole framework-derived rich-Zn-Co3O4/N-doped porous carbon with multiple enzyme-like activities for synergistic cancer therapy

Reactive oxygen species (ROS)-centered chemodynamic therapy (CDT) holds significant potential for tumor-specific treatment. However, insufficient endogenous H2O2 and extra glutathione within tumor microenvironment (TME) severely deteriorate the CDT's effectiveness. Herein, rich-Zn-Co3O4/N-doped porous carbon (Zn-Co3O4/NC) was fabricated by two-step pyrolysis, and applied to build high-efficiency nano-platform for synergistic cancer therapy upon combination with glucose oxidase (GOx), labeled Zn-Co3O4/NC-GOx for clarity. Specifically, the multiple enzyme-like activities of the Zn-Co3O4/NC were scrutinously investigated, including peroxidase-like activity to convert H2O2 to O2∙−, catalase-like activity to decompose H2O2 into O2, and oxidase-like activity to transform O2 to O2∙−, which achieved the CDT through the catalytic cascade reaction. Simultaneously, GOx reacted with intracellular glucose to produce gluconic acid and H2O2, realizing starvation therapy. In the acidic TME, the Zn-Co3O4/NC-GOx rapidly caused intracellular Zn2+ pool overload and disrupted cellular homeostasis for ion-intervention therapy. Additionally, the Zn-Co3O4/NC exhibited glutathione peroxidase-like activity, which consumed glutathione in tumor cells and reduced the ROS consumption for ferroptosis. The tumor treatments offer some constructive insights into the nanozyme-mediated catalytic medicine, coupled by avoiding the TME limitations.

Bimetallic PtPd Atomic Clusters as Apoptosis/Ferroptosis Inducers for Antineoplastic Therapy through Heterogeneous Catalytic Processes.

Active polymetallic atomic clusters can initiate heterogeneous catalytic reactions in the tumor microenvironment, and the products tend to cause manifold damage to cell metabolic functions. Herein, bimetallic PtPd atomic clusters (BAC) are constructed by the stripping of Pt and Pd nanoparticles on nitrogen-doped carbon and follow-up surface PEGylation, aiming at efficacious antineoplastic therapy through heterogeneous catalytic processes. After endocytosed by tumor cells, BAC with catalase-mimic activity can facilitate the decomposition of endogenous H2O2 into O2. The local oxygenation not only alleviates hypoxia to reduce the invasion ability of cancer cells but also enhances the yield of •O2- from O2 catalyzed by BAC. Meanwhile, BAC also exhibit peroxidase-mimic activity for •OH production from H2O2. The enrichment of reactive oxygen species (ROS), including the radicals of •OH and •O2-, causes significant oxidative cellular damage and triggers severe apoptosis. In another aspect, intrinsic glutathione (GSH) peroxidase-like activity of BAC can indirectly upregulate the level of lipid peroxides and promote ferroptosis. Such deleterious redox dyshomeostasis caused by ROS accumulation and GSH consumption also results in immunogenic cell death to stimulate antitumor immunity for metastasis suppression. Collectively, this paradigm is expected to inspire more facile designs of polymetallic atomic clusters in disease therapy.

PdMo nanoflowers for endogenous/exogenous-stimulated nanocatalytic therapy.

The clinical application of reactive oxygen species (ROS)-mediated tumor treatment has been critically limited by inefficient ROS generation. Herein, we rationally synthesized and constructed the three-dimensional PdMo nanoflowers through a one-pot solvothermal reduction method for elaborately regulated peroxidase-like enzymatic activity and glutathione peroxidase-like enzymatic activity, to promote oxidation ROS evolvement and antioxidation glutathione depletion for achieving intensive ROS-mediated tumor therapy. The three-dimensional superstructure composed of two-dimensional nanosheet subunits can solve the issues by avoiding the appearance of tightly stacked crystalline nanostructures. Significantly, Mo is chosen as a second metal to alloy with Pd because of its more chemical valence and negative ionization energy than Pd for improved electron transfer efficiencies and enhanced enzyme-like activities. In addition, the photothermal effect generated by PdMo nanoflowers could also enhance its enzymatic activities. Thus, this work provides a promising paradigm for achieving highly ROS-mediated tumor therapeutic efficacy by regulating the multi-enzymatic activities of Pd-based nanoalloys.

The One-Stop Integrated Nanoagent Based on Photothermal Therapy for Deep Infection Healing and Inflammation Inhibition.

Chronic wounds caused by bacterial infections are a major challenge in medical fields. The hypoxia condition extremely induces reactive oxygen species (ROS) generation and upregulates the expression of hypoxia-inducible factor, both of which can increase the pro-inflammatory M1 subtype macrophages production while reducing the anti-inflammatory M2 subtype macrophages. Besides, bacteria-formed biofilms can hinder the penetration of therapeutic agents. Encouraged by natural motors automatically executing tasks, hypothesized that supplying sufficient oxygen (O2 ) would simultaneously drive therapeutic agent movement, rescue the hypoxic microenvironment, and disrupt the vicious cycle of inflammation. Here, small organic molecule-based nanoparticles (2TT-mC6B@Cu5.4 O NPs) that possess high photothermal conversion efficiency and enzymatic activities are developed, including superoxide dismutase-, catalase-, and glutathione peroxidase-like activity. 2TT-mC6B@Cu5.4 O NPs exhibit superior ROS-scavenging and O2 production abilities that synergistically relieve inflammation, alleviate hypoxia conditions, and promote their deep penetration in chronic wound tissues. Transcriptome analysis further demonstrates that 2TT-mC6B@Cu5.4O NPs inhibit biological activities inside bacteria. Furthermore, in vivo experiments prove that 2TT-mC6B@Cu5.4 O NPs-based hyperthermia can effectively eliminate bacteria in biofilms to promote wound healing.

Glutathione Peroxidase-like Antioxidant Activity of 1,3-Benzoselenazoles: Synthesis and In Silico Molecular Docking Studies as Pancreatic Lipase Inhibitors.

The synthesis of 1,3-benzoselenazoles was achieved by the reaction of corresponding bis[3-amino-N-(p-tolyl)benzamide-2-yl] diselenide, bis[3-amino-N-(4-methoxyphenyl)benzamide-2-yl] diselenide, and bis[3-amino-N-(4-(dimethylamino)phenyl) benzamide-2-yl] diselenide with aryl aldehydes. The 1,3-benzoselenazoles continued to exist as planar molecules due to the presence of secondary Se···O interactions as revealed by the single-crystal X-ray analysis. The presence of secondary Se···O interactions in 1,3-benzoselenazoles was confirmed using natural bond orbital (NBO) and atoms in molecules (AIM) calculations. Nucleus-independent chemical shift (NICS) values suggested the presence of aromatic character in a five-membered benzoselenazole heterocyclic ring. The glutathione peroxidase (GPx)-like antioxidant activity of all 1,3-benzoselenazoles was assessed using a thiophenol assay, exhibiting greater antioxidant activity than Ph2Se2 used as a reference. The most active catalyst carrying a strong electron-donating group (-NMe2) at the ortho-position to the benzoselenazole ring was further investigated at different concentrations of thiophenol, H2O2, and 1,3-benzoselenazoles as catalyst for determining their catalytic parameters. Moreover, the potential applications of all 1,3-benzoselenazoles against pancreatic lipase (PL) have been identified using in silico interactions between the active sites of the 1LPB protein as evaluated using a molecular docking study.

Selenoneine-inspired selenohydantoins with glutathione peroxidase-like activity

Chronic diseases such as cystic fibrosis, inflammatory bowel diseases, rheumatoid arthritis, and cardiovascular illness have been linked to a decrease in selenium levels and an increase in oxidative stress. Selenium is an essential trace element that exhibits antioxidant properties, with selenocysteine enzymes like glutathione peroxidase being particularly effective at reducing peroxides. In this study, a series of synthetic organoselenium compounds were synthesized and evaluated for their potential antioxidant activities. The new selenohydantoin molecules were inspired by selenoneine and synthesized using straightforward methods. Their antioxidant potential was evaluated and proven using classical radical scavenging and metal-reducing methods. The selenohydantoin derivatives exhibited glutathione peroxidase-like activity, reducing hydroperoxides. Theoretical calculations using Density Functional Theory (DFT) revealed the selenone isomer to be the only one occurring in solution, with selenolate as a possible tautomeric form in the presence of a basic species. Cytocompatibility assays indicated that the selenohydantoin derivatives were non-toxic to primary human aortic smooth muscle cells, paving the way for further biological evaluations of their antioxidant activity. The results suggest that selenohydantoin derivatives with trifluoro-methyl (-CF3) and chlorine (-Cl) substituents have significant activities and could be potential candidates for further biological trials. These compounds may contribute to the development of effective therapies for chronic diseases such cardiovascular diseases.

Selenium-based nanozyme as a fluorescence-enhanced probe and imaging for chlortetracycline in living cells and foods

Developing rapid monitoring methods to detect antibiotic residues in food plays an important role in safeguarding human health. This study presents the development of a novel fluorescence-enhanced detection method for chlortetracycline (CTC) using a GSH-Se nanozyme. A GSH-Se nanozyme prepared using a one-pot hydrothermal method not only possesses excellent fluorescent properties but also exhibits good glutathione peroxidase-like activity. The results show that the addition of CTC leads to a significant enhancement in the fluorescence intensity of GSH-Se, and this increase exhibits a good linear relationship with the concentration of CTC. The linear range of this method is 0.02–1 µM, and the limit of detection (LOD) for CTC was 0.02 µM. Moreover, the cell toxicity of GSH-Se is low and can be used for monitoring and imaging of CTC in cells, and satisfactory results have been obtained in the analysis of actual food samples.

Multienzyme-Mimicking LaCoO3 Nanotrigger for Programming Cancer-Cell Pyroptosis.

Pyroptosis, a distinct paradigm of programmed cell death, is an efficient strategy against cancer by overcoming resistance to apoptosis. In this study, LaCoO3 (LCO) lanthanide-based nanocrystals with multienzyme characteristics are rationally designed and engineered to trigger the generation of cytotoxic reactive oxygen species (ROS) and the release of lanthanum ions, ultimately inducing lung cancer cell pyroptosis. The peroxidase- and oxidase-mimicking activities of LCO nanocrystals endow LCO with ROS production capacity in tumor tissues with an acidic pH and high hydrogen peroxide content. Concurrently, the LCO nanoenzyme exhibits catalase- and glutathione peroxidase-like activities, reversing the hypoxic microenvironment, destroying the activated antioxidant system of tumor cells, and amplifying the sensitivity of tumor cells to ROS. The use of ultrasound further accelerates the enzymatic kinetic rate. Most importantly, the La3+ ions released by LCO robustly destroy the lysosomal membrane, finally inducing canonical pyroptotic cell death, together with ROS. LCO-nanocrystal-triggered programmed cell pyroptosis amplifies the therapeutic effects both in vitro and in vivo, effectively restraining lung cancer growth and metastasis. This study paves a new avenue for the efficient treatment of lung cancer and metastasis through US-enhanced lanthanum-based nanoenzyme platforms and pyroptotic cell death.

Integrated Cascade Nanozymes with Antisenescence Activities for Atherosclerosis Therapy.

Senescent cells are the critical drivers of atherosclerosis formation and maturation. Mitigating senescent cells holds promise for the treatment of atherosclerosis. In an atherosclerotic plaque microenvironment, senescent cells interact with reactive oxygen species (ROS), promoting the disease development. Here, we hypothesize that a cascade nanozyme with antisenescence and antioxidant activities can serve as an effective therapeutic for atherosclerosis. An integrated cascade nanozyme with superoxide dismutase- and glutathione peroxidase-like activities, named MSe1 , is developed in this work. The obtained cascade nanozyme can attenuate human umbilical vein endothelial cell (HUVEC) senescence by protecting DNA from damage. It significantly weakens inflammation in macrophages and HUVECs by eliminating overproduced intracellular ROS. Additionally, the MSe1 nanozyme effectively inhibits foam cell formation in macrophages and HUVECs by decreasing the internalization of oxidized low-density lipoprotein. After intravenous administration, the MSe1 nanozyme significantly inhibits the formation of atherosclerosis in apolipoprotein E-deficient (ApoE-/- ) mice by reducing oxidative stress and inflammation and then decreases the infiltration of inflammatory cells and senescent cells in atherosclerotic plaques. This study not only provides a cascade nanozyme but also suggests that the combination of antisenescence and antioxidative stress holds considerable promise for treating atherosclerosis.

Sm/Co-Doped Silica-Based Nanozymes Reprogram Tumor Microenvironment for ATP-Inhibited Tumor Therapy.

Current applications of multifunctional nanozymes for reprogramming the redox homeostasis of the tumor microenvironment (TME) have been severely confronted with low catalytic activity and the ambiguity of active sites of nanozymes, as well as the stress resistance from the rigorous physical environment of tumor cells. Herein, the Sm/Co-doped mesoporous silica with 3PO-loaded nanozymes (denoted as mSC-3PO) are rationally constructed for simultaneously inhibiting energy production by ATP inhibitor 3PO and reprogramming TME by multi-activities of nanozymes with photothermal effect assist, i.e., enhanced peroxidase-like, catalase-like activity, and glutathione peroxidase-like activities, facilitating reactive oxygen species (ROS) generation, promoting oxygen content, and restraining the over-expressed glutathione. Through the optimal regulation of nanometric size and doping ratio, the fabricated superparamagnetic mSC-3PO enables the excellent exposure of active sites and avoids agglomeration owing to the large specific surface and mesoporous structure, thus providing adequate Sm/Co-doped active sites and enough spatial distribution. The constructed Sm/Co centers both participate in the simulated biological enzyme reactions and carry out the double-center catalytic process (Sm3+ and Co3+ /Co2+ ). Significantly, as the inhibitor of glycolysis, 3PO can reduce the ATP flow by cutting down the energy transform, thereby inhibiting tumor angiogenesis and assisting ROS to promote the early withering of tumor cells. In addition, the considerable near-infrared (NIR) light absorption of mSC-3PO can adapt to NIR excitable photothermal treatment therapy and photoexcitation-promoted enzymatic reactions. Taken together, this work presents a typical therapeutic paradigm of multifunctional nanozymes that simultaneously reprograms TME and promotes tumor cell apoptosis with photothermal assistance. This article is protected by copyright. All rights reserved.

N-Acetylcysteine-Derived Carbon Dots for Free Radical Scavenging in Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is associated with oxidative stress induced reactive oxygen species (ROS) dynamic equilibrium disturbance. Nanozymes, as nanomaterials with enzyme-like activity, can regulate intro-cellular ROS levels. In this study, a new carbon dots nanozyme, N-acetylcysteine-derived carbon dots (NAC-CDs), is developed and proved to be an ideal antioxidant and anti-senescent agent in IVDD management. The results confirmed the NAC-CDs have satisfactory biocompatibility and strong superoxide dismutase (250Umg-1 ), catalase, glutathioneperoxidase-like activity, and total antioxidant capacity. Then, the powerful free radical scavenging and antioxidant ability of NAC-CDs are demonstrated in vitro as observing the reduced ROS in H2 O2 induced senescent nucleus pulposus cells (NPCs), in which the elimination efficiency of toxic ROS is more than 90%. NAC-CDs also maintained mitochondrial homeostasis and suppressed cellular senescence, subsequently inhibited the expression of inflammatory factors in NPCs. In vivo, evaluations of imaging and tissue morphology assessments suggested that disc height index, magnetic resonance imaging grade and histological score are significantly improved from the degenerative models when NAC-CDs is applied. In conclusion, the study developed a novel carbon dots nanozyme, which efficiently rescues IVDD from ROS induced NPCs senescence and provides a potential strategy in management of IVDD in clinic.

Antioxidant Nanozymes: Mechanisms, Activity Manipulation, and Applications.

Antioxidant enzymes such as catalase, superoxide dismutase, and glutathione peroxidase play important roles in the inhibition of oxidative-damage-related pathological diseases. However, natural antioxidant enzymes face some limitations, including low stability, high cost, and less flexibility. Recently, antioxidant nanozymes have emerged as promising materials to replace natural antioxidant enzymes for their stability, cost savings, and flexible design. The present review firstly discusses the mechanisms of antioxidant nanozymes, focusing on catalase-, superoxide dismutase-, and glutathione peroxidase-like activities. Then, we summarize the main strategies for the manipulation of antioxidant nanozymes based on their size, morphology, composition, surface modification, and modification with a metal-organic framework. Furthermore, the applications of antioxidant nanozymes in medicine and healthcare are also discussed as potential biological applications. In brief, this review provides useful information for the further development of antioxidant nanozymes, offering opportunities to improve current limitations and expand the application of antioxidant nanozymes.

Turning carbon dots into selenium bearing nanoplatforms with in vitro GPx-like activity and pro-oxidant activity

Selenium (Se) has been defined as the “Janus element”, with one face showing antioxidant activity and the other pro-oxidant activity. The biological effect of Se depends on both dose and speciation. Se nanoparticles are attracting major interest, although their large-scale preparation for biomedical applications is not trivial. We hypothesize that acid anhydride-coated carbon dots (AA-CD) are an attractive platform for preparing nanoparticles containing chemically defined Se. The reaction of AA-CD with 3-selenocyanatopropan-1-amine yields carbon dots bearing selenocyanate and carboxylate groups (CD-SeCN) that allow for tuning the hydrosolubility. CD-SeCN has a Se content of 0.36 µmol per mg of nanoparticles, and they show the typical photoluminescence of carbon dots. The selenocyanate groups (SeCN) exhibited glutathione peroxidase-like activity and cytotoxicity. Data show that antioxidant behavior differs between normal and tumor cells, and the evaluation on HEK293 and A549 cells reveals that the toxicity of CD-SeCN depends on dose, time, and intracellular glutathione (GSH) content. The toxicity of CD-SeCN decreases with the time of incubation and the cell death mechanism switches from necrosis to apoptosis, indicating that CD-SeCN is neutralized. Additionally, high levels of intracellular GSH exert a protective effect. These results support a pharmacological potential in cancers with low levels of intracellular GSH. The use of AA-CD as nanoplatforms is a general strategy that paves the way for the engineering of advanced nanosystems.

Mn3 O4 Nanoshell Coated Metal-Organic Frameworks with Microenvironment-Driven O2 Production and GSH Exhaustion Ability for Enhanced Chemodynamic and Photodynamic Cancer Therapies.

Nanomedicine exhibits emerging potentials to deliver advanced therapeutic strategies in the fight against triple-negative breast cancer (TNBC). Nevertheless, it is still difficult to develop a precise codelivery system that integrates highly effective photosensitizers, low toxicity, and hydrophobicity. In this study, PCN-224 is selected as the carrier to enable effective cancer therapy through light-activated reactive oxygen species (ROS) formation, and the PCN-224@Mn3 O4 @HA is created in a simple one-step process by coating Mn3 O4 nanoshells on the PCN-224 template, which can then be used as an "ROS activator" to exert catalase- and glutathione peroxidase-like activities to alleviate tumor hypoxia while reducing tumor reducibility, leading to improved photodynamic therapeutic (PDT) effect of PCN-224. Meanwhile, Mn2+ produced cytotoxic hydroxyl radicals (∙OH) via the Fenton-like reaction, thus producing a promising spontaneous chemodynamic therapeutic (CDT) effect. Importantly, by remodeling the tumor microenvironment(TME), Mn3 O4 nanoshells downregulated hypoxia-inducible factor 1α expression, inhibiting tumor growth and preventing tumor revival. Thus, the developed nanoshells, via light-controlled ROS formation and multimodality imaging abilities, can effectively inhibit tumor proliferation through synergisticPDT/CDT, and prevent tumor resurgence by remodeling TME.

Shell-core COF@Co3O4 Z-scheme heterojunctions for triple amplification of oxidative stress to enhance nanocatalytic-sonodynamic tumor therapy

Constructing efficient nanozyme platforms with multiple amplification of tumor oxidative stress is crucial to enhance the reactive oxygen species (ROS)-mediated tumor therapy. However, the inherent low catalytic activity and unsustainability of nanozymes in the highly complex tumor microenvironment (TME) severely restricted their clinical applications. Herein, we first reported a heterojunction (HJ)-enhanced nanocatalytic-sonodynamic therapy nanoplatform based on COF@Co3O4 Z-scheme HJs with shell-core architecture by coating COF on the surface of Co3O4 nanospheres. The as-prepared Co3O4 nanospheres not only exhibited excellent sonodynamic properties owing to the narrow bandgap (1.37 eV), but also possessed peroxidase-like, catalase-like, and glutathione peroxidase-like catalytic activities to realize the amplification of ROS levels and relieve tumor hypoxia due to the presence of multivalent Co element. More importantly, the ultrasound (US)-triggered ROS generation ability and triple enzyme-mimic activity of Co3O4 nanospheres were greatly enhanced by the encapsulation of COF to fabricate Z-scheme HJs with large interfacial contact area. Based on the improved spatial separation dynamics of US-generated electron-hole pairs and accelerate carrier transfer process, complete tumor eradication without recurrence was realized by the synergetic therapeutic effect of COF@Co3O4 through HJ-enhanced nanocatalytic-sonodynamic therapy. This work presents highly efficient nanozyme platforms with both multiple enzyme-mimic catalytic activity and sonodynamic properties, which will open up a promising approach to engineer semiconductor Z-scheme HJs for enhanced tumor therapy.

3,3'-Diselenodipropionic acid immobilised gelatin gel: a biomimic catalytic nitric oxide generating material for topical wound healing application.

Nitric oxide (NO) plays a pivotal role in the wound healing process and promotes the generation of healthy endothelium. In this work, a simple method has been developed for fabricating a diselenide grafted gelatin gel, which reduces NO donors such as S-nitroso-N-acetylpenicillamine (SNAP) by glutathione peroxidase-like mechanism to produce NO. Briefly, the process involved covalently conjugating 3,3'-diselenodipropionic acid (DSePA) with gelatin via carbodiimide coupling. The resulting gelatin-DSePA conjugate (G-Se-Se-G) demonstrated NO production upon incubation with SNAP and glutathione (GSH) with the flux of 4.8 ± 0.6 nmol cm-2 min-1 and 1.6 ± 0.1 nmol cm-2 min-1 at 10 min and 40 min, respectively. The G-Se-Se-G recovered even after 5 days of incubation with the reaction mixture retaining catalytic activity up to 74%. Subsequently, G-Se-Se-G was suspended (5% w/v) in water with lecithin (6% w/w of gelatin) and F127 (3% w/w of gelatin) to prepare gel through temperature dependant gelation method. The fabricated G-Se-Se-G gel exhibited desirable rheological characteristics and excellent mechanical stability under storage conditions and did not cause any significant toxicity in normal human keratinocytes (HaCaT) and fibroblast cells (WI38) up to 50 μg ml-1 of selenium equivalent. Finally, mice studies confirmed that topically applied G-Se-Se-G gel and SNAP promoted faster epithelization and collagen deposition at the wound site. In conclusion, the development of a biomimetic NO generating gel with sustained activity and biocompatibility was achieved.

Fe/Cu-AuNP nanocomposites as enzyme-like catalysts to modulate the tumor microenvironment for enhanced synergistic cancer therapy.

The intensive investigation of chemodynamic therapy (CDT) for tumor eradication revealed that the therapeutic effects of this ROS-mediated therapy are limited by endogenous reductants and inefficient Fenton-like reactions. In this study, we developed a new Fe/Cu-AuNP-PEG nanocomposite to enhance CDT and provide a synergistic treatment for tumors. The Fe/Cu-AuNP-PEG nanocomposite demonstrated effective ˙OH production and high photothermal conversion efficiency under 808 nm illumination, which promoted the ˙OH production, thereby enhancing the CDT efficacy and exhibiting a synergistic treatment for cancer. More importantly, the Fe/Cu-AuNP-PEG nanocomposite showed the ability to deplete GSH and catalyze glucose to generate H2O2, which facilitated the Fenton-like reaction and reduced the antioxidant properties of tumors, further improving the efficacy of CDT. Therefore, the Fe/Cu-AuNP-PEG nanocomposite, with horseradish peroxidase-like, glutathione peroxidase-like, and glucose oxidase-like activities, is a promising anti-tumor agent for integrating enhanced CDT and photothermal therapy (PTT) with the enhancement of synergistic therapeutic effects.