Glucose Oxidase Loading Research Articles

A biomineralized bi-functional hybrid nanoflower to effectively combat bacteria via a glucose-powered cascade catalytic reaction.

The bacterial resistance due to the abuse of conventional antibiotics is regarded as a major problem for bacterial-induced infections and chronic wound healing. There is an urgent need to explore alternative antimicrobial strategies and functional materials with excellent antibacterial efficacy. Herein, guanosine monophosphate (GMP) and glucose oxidase (GOD) were coordinated with copper ions to obtain a bi-functional hybrid nanoflower (Cu-GMP/GODNF) as a cascade catalyst for promoting antibacterial efficacy. Besides the efficient conversion of glucose to hydrogen peroxide, the produced gluconic acid by loading GOD can supply a compatible catalytic environment to substantially improve the peroxidase activity for generating more toxic reactive oxygen species (ROS). So, the glucose-powered cascade catalytic reaction effectively killed bacteria. Moreover, H2O2 self-supplied by glucose can reduce harmful side effects of exogenous H2O2. Meanwhile, the adhesion between the Cu-GMP/GODNF and the bacterial membrane can enhance the antibacterial efficacy. Therefore, the achieved bi-functional hybrid nanoflower exhibited high efficiency and biocompatibility for killing bacteria in diabetes-related infections.

Photothermal-triggered release of alkyl radicals and cascade generation of hydroxyl radicals via a versatile hybrid nanocatalyst for hypoxia-irrelevant synergistic antibiofilm therapy

Well-designed nanocatalysts capable of generating free radicals have recently shown promising potential for treating bacterial biofilm infections. However, the biofilm microenvironments such as hypoxia and over-expressed glutathione (GSH) seriously limit their biomedical applications. To address these issues, we herein construct a dual free radical nanogenerator (MnO2/GOx/AIBI) by loading glucose oxidase (GOx) and thermal-labile azo initiator (AIBI) onto the flower-like MnO2 with high loading capacity for the hypoxia-irrelevant treatment of biofilm-associated bacterial infections. On the one hand, MnO2/GOx/AIBI nanocomposites can generate hydroxyl radicals by glucose-fueled cascade catalytic reactions between GOx and MnO2 for efficient O2– and H2O2-self-supplying chemodynamic therapy (CDT). On the other hand, MnO2 can provide local photonic hyperpyrexia, which not only triggers the O2-independent generation of alkyl radicals for photothermal dynamic therapy (PTDT), but also enhances the CDT efficacy by accelerating the release of Fenton-type Mn2+. Besides, MnO2 can degrade GSH over-expressed in the infection sites, improving the synergistic CDT/PTDT therapeutic effectiveness by redox dyshomeobasis. The hybrid MnO2/GOx/AIBI nanocatalysts exhibit satisfactory in vitro and in vivo antibacterial and antibiofilm performances with minimal toxic side effects. Taken together, the developed hypoxia-irrelevant dual-mode synergistic antibacterial nanoplatform can effectively overcome the interferences of biofilm microenvironments, showing a promising potential for future biomedical applications.

Construction nanoenzymes with elaborately regulated multi-enzymatic activities for photothermal-enhanced catalytic therapy of tumor

In order to solve the limitation of tumor microenvironment on the anticancer effect of nanozymes, a multifunctional nanoenzyme Co/La-PB@MOF-199/GOx was designed in this work. By doping Co2+ and La3+ in different proportions, Co/La-PB with the optimal photothermal-enhanced catalytic performance was screened, which can catalyze H2O2 to generate more hydroxyl radicals (•OH) and oxygen, showing peroxidase (POD)-like and catalase(CAT)-like property. Through MOF-199 coating and loading glucose oxidase (GOx), a multifunctional nanoenzyme Co/La-PB@MOF-199/GOx was achieved. Due to the pH response of MOF-199, GOx can be accurately released into tumors to catalyze the reaction of glucose and oxygen to produce H2O2. In this process, the oxygen consumption can be compensated by the CAT-like property to realize continuous consumption of glucose and self-supply of H2O2 to continuously produce •OH. In the presence of high oxidation state metal ions (Co3+ and Fe3+), GSH consumption is accelerated to avoid weakening of •OH, showing the glutathione oxidase (GPx-like) activity. Besides, magnetic resonance imaging (MRI) experiments showed the potential application in imaging guided therapy. In vivo anti-tumor experiments showed a satisfactory anti-cancer effect through multi-enzymatic activities.

Confined Construction of Ultrasmall Molybdenum Disulfide-Loaded Porous Silica Particles for Efficient Tumor Therapy.

Recently, molybdenum sulfide (MoS2) has shown great application potential in tumor treatment because of its good photothermal properties. Unfortunately, most of the current molybdenum disulfide-based nanotherapeutic agents suffer from complex preparation processes, low photothermal conversion efficiencies, and poor structural/compositional regulation. To address these issues, in this paper, a facile "confined solvothermal" method is proposed to construct an MoS2-loaded porous silica nanosystem (designated as MoS2@P-hSiO2). The maximum photothermal efficiency of 79.5% of molybdenum-based materials reported in the literature at present was obtained due to the ultrasmall MoS2 nanoclusters and the rich porous channels. Furthermore, both in vitro and in vivo experiments showed that the cascade hybrid system (MoS2/GOD@P-hSiO2) after efficient loading of glucose oxidase (GOD) displayed a significant tumor-suppressive effect and good biosafety through the combined effects of photothermal and enzyme-mediated cascade catalytic therapy. Consequently, this hybrid porous network system combining the in situ solvothermal strategy of inorganic functional components and the efficient encapsulation of organic enzyme macromolecules can provide a new pathway to construct synergistic agents for the efficient and safe treatment of tumors.

Highly Efficient GSH-Responsive "Off-On" NIR-II Fluorescent Fenton Nanocatalyst for Multimodal Imaging-Guided Photothermal/Chemodynamic Synergistic Cancer Therapy.

Accurate diagnosis and effective treatment of malignant tumors under the interference of complex and diverse tumor microenvironments (TMEs) have become the focus of research. Herein, an innovative TME-activated biomimetic nanocatalyst with quad-modal imaging capabilities of second near-infrared (NIR-II) "turn-on" fluorescence imaging, magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and photothermal imaging (PTI) was designed and developed for self-enhanced photothermal/chemodynamic synergistic therapy. The catalyst was fabricated by loading glucose oxidase (GOD) and Ag2S quantum dots (QDs) on MnO2 nanosheets and coating them with a 4T1 cell membrane (AMG@CM), which enables them to successfully escape immune clearance and have appealing tumor-targeting ability and biocompatibility. The NIR-II fluorescence at 1130 nm of Ag2S QDs quenched by MnO2 could be recovered in vivo through the glutathione (GSH)-induced degradation of MnO2, enabling excellent TME-responsive tumor visualization. Simultaneously, the released Mn2+ can catalyze H2O2 to produce abundant hydroxyl radicals (•OH), achieving photothermal synergistically enhanced chemodynamic therapy (CDT) under NIR-II radiation. Moreover, the CDT could be self-enhanced by GOD due to the extra produced H2O2. This work demonstrates a novel and highly efficient multimodal imaging-guided integrated treatment strategy for dual-enhanced CDT tumor precise diagnosis and treatment.

Impedance Characterization of OECT Behavior in Enzyme-Embedded Conductive Polymer Matrix

Latest generation glucose sensors use small-form wearables which provide continuous data. Thesedevices represent the commercial forefront aiming towards personalized and real-time point-of-carebiomedical applications. Currently, device lifetimes are limited due to unknown failure mechanisms andex-situ calibration strategies. Creating a method for in-situ sensor diagnostics will allow a bottom-upapproach for designing enzyme-supporting matrixes and calibration strategies inherent to biosensors. Tothis end, this work seeks to enhance the understanding of performance, stability, and failure mechanismsof biologically based electrochemical transistors using impedimetric measurements.Here, we reveal the fundamental interplay between glucose oxidase loading and the electronic propertiesof a commonly used PEDOT:PSS matrix as an encapsulating medium. Fundamental to these studies wasthe discovery of conductivity enhancing strategies compatible with preserving enzyme activity. Theenzyme-embedded conductive polymer matrix was used in an organic electrochemical transistor probedvia electrochemical impedance (EI) to determine the causes of performance loss over sensor lifetimes.Supporting spectroscopies aided in detailing film morphology and electrical property changes associatedwith sensor behavior.

Novel YOF-Based Theranostic Agents with a Cascade Effect for NIR-II Fluorescence Imaging and Synergistic Starvation/Photodynamic Therapy of Orthotopic Gliomas.

Accurate diagnosis and highly effective treatment of glioblastoma are still challenges in clinic. Near-infrared (NIR) light triggered fluorescence imaging and photodynamic therapy (PDT) showed the potential for theranostics of glioblastoma, but the presence of blood-brain barrier (BBB) and hypoxia limited treatment effect. Herein, the novel theranostic nanoagents with YOF:Nd3+ as core, MnO2 as shell, and further loading photosensitizer (indocyanine green, ICG) and glucose oxidase (GOx) were successfully constructed, and further modified with lactoferrin to endow them with BBB penetration and target abilities (YOF:Nd3+@MnO2-ICG-GOx-LF, YMIGL). The YOF:Nd3+ core with good fluorescence performances makes YMIGL act as promising probes for fluorescence imaging in the second biowindow (NIR-II FL). The combination of GOx and MnO2 shell significantly increased the O2 generation from the cascade reactions and consumed glucose, improving the treatment effect of PDT and achieving starvation treatment (ST). These theranostic nanoagents exhibit a highly efficient inhibition effect on orthotopic gliomas by cascade reactions, which improved PDT and ST.

Cheap and Sustainable Biosensor Fabrication by Enzyme Immobilization in Commercial Polyacrylic Acid/Carbon Nanotube Films

Novel glucose biosensors were constructed by loading glucose oxidase (GOx) into the nanopores of homogenous carbon nanotube (CNT) films on the surface of Pt disk electrodes and trapping the enzyme by subsequent deposition of polyacrylic acid (PAA), forming PAA/GOx-CNT-modified Pt disks. In amperometric biosensing with anodic hydrogen peroxide (H2O2) detection at a potential of +600 mV, increasing electrolyte glucose concentrations produced instantaneous steps in the H2O2 oxidation current. Glucose biosensor amperometry was feasible down to 10 μM, with a sensitivity of about 34 μA mM–1 cm–2 and linear current response up to 5 mM. The biosensors reliably determined glucose concentrations in human serum and a beverage. Successful trials with PAA/GOx-CNT-modified screen-printed Pt electrode disks demonstrated the potential of this means of enzyme fixation in biosensor mass fabrication, which offers a unique combination of cheap availability of the two matrix constituents and sensor layer formation through simple drop-and-dry steps. PAA/GOx-CNT/Pt biosensors are green and user-friendly bioanalytical tools that do not need large budgets, special skills, or laboratory amenities for their production. Any user, from industrial, university, or school laboratories, even if inexperienced in biosensor construction, can prepare functional biosensors with GOx, as in these proof-of-principle studies, or with other redox enzymes, for clinical, environmental, pharmaceutical, or food sample analysis.

Donor-acceptor structured photothermal COFs for enhanced starvation therapy

Targeted delivery of adequate glucose oxidase (GOX) into tumor cells by covalent organic frameworks (COFs) remains a great challenge due to their insolubility and easy aggregation. Herein, an effective strategy to synthesize nanosized donor–acceptor (D-A) structured COFs with tunable sizes, long-time water-dispersibility and special selectivity was developed. Designed D-A structure provided pathways and channels for effective charge carriers transport, and this endowed COFs with excellent photothermal property to greatly enhance starvation therapy efficiency. Large surface area and porosity in the cross-linked crystal allowed high GOX loading capacity, and further surface modification with biomolecules made it possess colloid-like water stability and targeted selectivity. All these good properties guaranteed much better in vivo and in vitro tumor ablation than single therapy, and outstanding anti-migration results were also achieved. Detailed cell apoptosis study indicated the combined therapy effectively produced reactive oxygen species, and apoptosis was induced by endogenous mitochondrial apoptosis pathway and Caspase-3 activation process, finally making cancer cells more sensitive to inadequate energy supply and high temperature. This work developed a new strategy to synthesize D-A structured photothermal COFs with good dispersibility and greatly enhance starvation therapy without any additional use of chemical drugs.

A Photoelectrochemical Platform Based on Polyaniline-Modified Titanium Dioxide Facet Heterostructure

A photoelectrochemical (PEC) electrode for glucose detection was built based on polyaniline (PANI) modified titanium dioxide heterojunction (FH-TiO2) structures. Ultrathin titanium dioxide (TiO2) nanosheets are assembled onto rutile nanorods (TiO2 NRs). Experiments show that the main exposed faces of these nanosheets are (101) or (111) crystal planes. Proven by theoretical calculation, the bottom of the conduction band (CB) of (111) is 0.15 eV lower than the bottom of the conduction band of (101). Therefore, when the material is excited by light, photogenerated electrons are able to transfer from the conduction band of (101) to the conduction band of (111). PANI was introduced as a medium to effectively conduct photogenerated charges between glucose oxidase and titanium dioxide. A photoelectric detection electrode for glucose was fabricated by loading glucose oxidase onto PANI@FH-TiO2. This electrode showed excellent performance in 0.2-1.0 mM linear range with a sensitivity 15.63 μA mM-1 cm-2 and 1.0-15.0 mM linear range with a sensitivity of 1.42 μA mM-1 cm-2.

Glucose-responsive multifunctional metal–organic drug-loaded hydrogel for diabetic wound healing

As the incidence of diabetes increases, its complication, diabetic foot ulcers, has become the main type of clinically chronic refractory wounds. Due to the hyperglycemic microenvironment of the diabetic wound, which leads to vascular defects and bacterial growth, the therapeutic effect of wound dressings lacking strategic design is relatively limited. In this study, we designed an injectable, “self-healing”, and glucose-responsive multifunctional metal–organic drug-loaded hydrogel (DG@Gel) for diabetic wound healing. The functionalized hydrogel was prepared by phase-transfer-mediated metallo-nanodrugs, which were made by co-assembling zinc ions, organic ligands, and a small-molecule drug, deferoxamine mesylate (DFO), and the programmed loading of glucose oxidase (GOX). When injected into a diabetic wound, the GOX in DG@Gel changed the hyperglycemic wound microenvironment by decomposing excess glucose into hydrogen peroxide and glucuronic acid, which decreased the pH of the wound site. The low pH promoted the release of zinc ions and DFO, which exhibited synergistic antibacterial and angiogenesis activity for diabetic wound repair. In vitro experiments revealed the antibacterial activity and the cell proliferation, migration, and tube formation ability of DG@Gel. Moreover, in vivo experiments showed that DG@Gel can induce re-epithelialization, collagen deposition, and angiogenesis during wound healing in diabetic mice with good biocompatibility and biodegradability. The results suggest that this hydrogel is a promising innovative dressing for the treatment of diabetic wounds. Statement of significanceDiabetic ulcers, as one of the main types of chronic refractory wounds, are not treated effectively in the clinic due to a lack of strategic approach. In this study, we designed a glucose-responsive multifunctional metal–organic drug-loaded hydrogel (DG@Gel), which can change the hyperglycemic wound microenvironment by decomposing excess glucose into hydrogen peroxide and glucuronic acid. This in turn promoted the release of zinc ions and deferoxamine mesylate (DFO) in the hydrogel, which exhibited synergistic antibacterial and angiogenic activity for diabetic wound repair. Furthermore, the DG@Gel exhibited good biocompatibility and biodegradability in vivo. In general, this innovative strategy design may have great application potential in the treatment of various chronic wounds.

Artificial blood vessel biofuel cell for self-powered blood glucose monitoring

Biofuel cell (BFC) is a kind of bio-cell based on biological enzymes. The enzyme as a catalyst can interconvert renewable and sustainable energy into each other more rapidly, such as the biochemical energy in glucose and ethanol into electrical energy. In this work, artificial blood vessel and fuel cell are based on polyaniline/thermoplastic polyurethane (PANI/TPU) fiber membrane with an average fiber diameter of 1300 nm, a film thickness of 167 μm, and a permeability of 18.4 mm s−1. The PANI/TPU fiber membrane was prepared by electrospinning and followed in situ polymerization. The membrane has good flexibility and mechanical properties, and can be stretched up to 200%. The advantages of good hydrophilicity, biocompatibility and high porosity make it possible to efficiently load glucose oxidase and laccase. The prepared BFC can stably output a voltage of 50 mV in simulated blood, and the output electrical signal changes significantly with the change of glucose concentration, which may be used in implantable devices or blood glucose monitoring.

Construction of a Mesoporous Ceria Hollow Sphere/Enzyme Nanoreactor for Enhanced Cascade Catalytic Antibacterial Therapy.

Nanozyme has been regarded as one of the antibacterial agents to kill bacteria via a Fenton-like reaction in the presence of H2O2. However, it still suffers drawbacks such as insufficient catalytic activity in near-neutral conditions and the requirement of high H2O2 levels, which would minimize the side effects to healthy tissues. Herein, a mesoporous ceria hollow sphere/enzyme nanoreactor is constructed by loading glucose oxidase in the mesoporous ceria hollow sphere nanozyme. Due to the mesoporous framework, large internal voids, and high specific surface area, the obtained nanoreactor can effectively convert the nontoxic glucose into highly toxic hydroxyl radicals via a cascade catalytic reaction. Moreover, the generated glucose acid can decrease the localized pH value, further boosting the peroxidase-like catalytic performance of mesoporous ceria. The generated hydroxyl radicals could damage severely the cell structure of the bacteria and prevent biofilm formation. Moreover, the in vivo experiments demonstrate that the nanoreactor can efficiently eliminate 99.9% of bacteria in the wound tissues and prevent persistent inflammation without damage to normal tissues in mice. This work provides a rational design of a nanoreactor with enhanced catalytic activity, which can covert glucose to hydroxyl radicals and exhibits potential applications in antibacterial therapy.

One-Pot Approach to Fe2+ /Fe3+ -Based MOFs with Enhanced Catalytic Activity for Fenton Reaction.

Smart theragnostic nanoplatforms exhibit great promise in clinical tumor treatment. The Fe-based Fenton reaction in tumor sites may generate reactive oxygen species to kill cancer cells with negligible side effects on normal tissues. However, its efficiency and duration are limited by the low intracellular concentration of H2 O2 , weak acidicity of tumor tissue, and low catalytic activity of conventional Fenton reagents. Herein, a facile strategy is proposed to efficiently overcome these obstacles. An efficient enzymatic/Fenton-starvation nanoreactor PMs loaded with glucose oxidase and perfluoropentane (PGPMs) is constructed through synthesizing methoxy-PEG-carboxymethy-modified iron (Fe2+ /Fe3+ )-based metal-organic frameworks (PMs), followed by loading glucose oxidase (GOx) and perfluoropentane (PFP). PGPMs accumulating in the tumor tissue exhibit tumor microenvironment-responsive biodegradable behavior and unusual catalytic activity for Fenton reaction advantageous over Fe3+ -based MOFs. Meanwhile, encapsulation of GOx into PGPMs further significantly increases the catalytic activity for Fenton reaction and also induces starvation therapy. PGPMs also exhibit considerable capabilities of ultrasound and tumor microenvironment-responsive T2 MR imaging applicable for contrast-enhanced diagnosis. Both in vitro and in vivo studies demonstrate the great diagnostic and therapeutic potentials of this nanoreactor in tumor.

Ionic Covalent-Organic Framework Nanozyme as Effective Cascade Catalyst against Bacterial Wound Infection.

The increasing resistance risks of conventional antibiotic abuse and the formed biofilm on the surface of wounds have been demonstrated to be the main problems for bacteria-caused infections and unsuccessful wound healing. Treatment by reactive oxygen species, such as the commercial H2 O2 , is a feasible way to solve those problems, but limits in its lower efficiency. Herein, an ionic covalent-organic framework-based nanozyme (GFeF) with self-promoting antibacterial effect and good biocompatibility has been developed as glucose-triggered cascade catalyst against bacterial wound infection. Besides the efficient conversion of glucose to hydrogen peroxide, the produced gluconic acid by loading glucose oxidase can supply a compatible catalytic environment to substantially improve the peroxidase activity for generating more toxic hydroxyl radicals. Meanwhile, the adhesion between the positively charged GFeF and the bacterial membrane can greatly enhance the healing effects. This glucose-triggered cascade strategy can reduce the harmful side effects by indirectly producing H2 O2 , potentially used in the wound healing of diabetic patients.

Sulfite‐Inserted MgAl Layered Double Hydroxides Loaded with Glucose Oxidase to Enable SO2‐Mediated Synergistic Tumor Therapy

AbstractAs a type of unique gaseous molecules, SO2 presents capabilities in the feasible cellular influx and the induction of apoptosis by generating intracellular toxic radicals. Developing therapeutic platforms to enable effective SO2 gas release at the tumor site is highly demanded in the exploration of more “green” and effective treatment protocols for cancer therapy but remains challenging. Here for the first time, fine nanosheets composing of Mg‐Al layered double hydroxides (MgAl LDH) are synthesized and inserted with sulfite in its layered structures (MgAl‐SO3 LDH). After the loading of glucose oxidase (GOx/MgAl‐SO3 LDH), the composite nanosheets present the controllable SO2 gas release in an acidic responsive manner. Owing to the glycolysis effect of GOx, the gluconic acid generated agitates the intracellular SO2 release from nanosheets, and excessive H2O2 reacts with SO2 effectively and facilitates the production of toxic radicals, inducing remarkable oxidative damages to tumor cells. Meanwhile, the consumption of intracellular glucose by GOx/MgAl‐SO3 LDH depletes the energy supply of tumor cells, favoring the tumor inhibition both in vitro and in vivo in a synergistic fashion. Therefore, this study has provided distinctive perspectives in the exploration of therapeutic platforms with green functionalities and biodegradability for effective tumor treatment.

An Electrochemical Sensor Based on Redox-Active Schiff Base Polymers for Simultaneous Sensing of Glucose and pH

A novel redox-active Schiff base polymer (SBPPPDA-PDA) was prepared by condensation of p-phenylenediamine with 1,10-phenanthroline-2,9-dicarbaldehyde. The structure of SBPPPDA-PDA was investigated by scanning electron microscopy, transmission electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy, N2 adsorption/desorption isotherm, and powder X-ray diffraction and electrochemical techniques. The results showed that SBPPPDA-PDA had two-dimensional lamellar structure. The electrochemical properties of SBPPPDA-PDA were characterized by cyclic voltammetry, showing several pairs of redox peaks and good catalytic ability toward oxygen reduction. On the basis of the redox-active activity of SBPPPDA-PDA, an electrochemical pH sensor was proposed based on SBPPPDA-PDA with a linear range from 2 to 9 for pH detection. With nitrogen-containing skeleton and porous structure, SBPPPDA-PDA could be used as support to load glucose oxidase (GOD). Thus, a novel ratiometric electrochemical glucose sensor was further constructed by immobilizing GOD on SBPPPDA-PDA modified electrode. The results revealed that the reduction peak of O2 decreased with the gradual addition of glucose, while the response peak of SBPPPDA-PDA at about 0.15 V almost remained. The sensor based on GOD/SBPPPDA-PDA/SPE showed a rapid response, a linear range from 22.5 μmol/L–5 mmol/L and a lower detection limit of 7.56 μmol/L for glucose.

Ferrocene-containing polymersome nanoreactors for synergistically amplified tumor-specific chemodynamic therapy

Chemodynamic therapy (CDT) has been proposed to convert tumoral H2O2 into toxic hydroxyl radicals (OH) via Fenton or Fenton-like reactions for antitumor efficacy, which is frequently limited by low H2O2 concentrations or lack of enough metal ions inside tumor tissues. In this report, we present ferrocene-containing responsive polymersome nanoreactors via loading glucose oxidase (GOD) and hypoxia-activable prodrug tirapazamine (TPZ) in the inner aqueous cavities. After intravenous injection, the polymersome nanoreactors with the optimized nanoparticle size of ~100 nm and poly(ethylene glycol) corona facilitate tumor accumulation. The tumor acidic microenvironment can trigger the permeability of the polymersome membranes to activate the nanoreactors and release the loaded TPZ prodrugs. Tumor oxygen and glucose can enter the polymersome nanoreactors and are transformed into H2O2 under the catalysis of GOD, which are further converted into OH via Fenton reaction under catalysis of ferrocene moieties. The oxygen consumption can aggravate tumor hypoxia to activate hypoxia-responsive TPZ prodrugs which can produce benzotriazinyl (BTZ) radicals and OH. All the produced radicals synergistically kill tumor cells via the amplified CDT and suppress the tumor growth efficiently. Thus, the ferrocene-containing responsive polymersome nanoreactors loading GOD and TPZ represent a potent nanoplatform to exert amplified CDT for improved anticancer efficacy.

Hypoxia modulation by dual-drug nanoparticles for enhanced synergistic sonodynamic and starvation therapy

BackgroundSonodynamic therapy (SDT) is an emerging non-invasive therapeutic technique. SDT-based cancer therapy strategies are presently underway, and it may be perceived as a promising approach to improve the efficiency of anti-cancer treatment. In this work, multifunctional theranostic nanoparticles (NPs) were synthesized for synergistic starvation therapy and SDT by loading glucose oxidase (GOx, termed G) and 5,10,15,20-tetrakis (4-chlorophenyl) porphyrin) Cl (T (p-Cl) PPMnCl, termed PMnC) in Poly (lactic-co-glycolic) acid (PLGA) NPs (designated as MG@P NPs).ResultsOn account of the peroxidase-like activity of PMnC, MG@P NPs can catalyze hydrogen peroxide (H2O2) in tumor regions to produce oxygen (O2), thus enhancing synergistic therapeutic effects by accelerating the decomposition of glucose and promoting the production of cytotoxic singlet oxygen (1O2) induced by ultrasound (US) irradiation. Furthermore, the NPs can also serve as excellent photoacoustic (PA)/magnetic resonance (MR) imaging contrast agents, effectuating imaging-guided cancer treatment.ConclusionMultifunctional MG@P NPs can effectuate the synergistic amplification effect of cancer starvation therapy and SDT by hypoxia modulation, and act as contrast agents to enhance MR/PA dual-modal imaging. Consequently, MG@P NPs might be a promising nano-platform for highly efficient cancer theranostics.Graphical

Enzyme hybrid virus-like hollow mesoporous CuO adhesive hydrogel spray through glucose-activated cascade reaction to efficiently promote diabetic wound healing

Diabetic wounds characterized by impaired healing due to uncontrolled and interrelated bacterial infection, reduced vascularization and hypoxia microenvironment, remain a worldwide challenge. Copper ions have been proved to stimulate angiogenesis to improve chronic wound healing, and copper oxide nanoparticles have been widely investigated for bacterial elimination. Herein, we constructed an adhesive hydrogel spray with loading glucose oxidase hybrid virus-like hollow mesoporous CuO nanospheres to efficiently promote diabetic wound healing. Under local hyperglycemia in bacterial biofilm, CuO nanospheres can be decomposed to convert the glucose degradation, produce H2O2 to generate toxic •OH for antibacterial usage, then the simultaneously released Cu2+ can induce the proliferation and migration of keratinocytes and tubule formation of endothelial cells. More importantly, after bacterial eradication within inflammatory phase of wound healing, CuO nanospheres can act as catalase-mimic agents to produce massive O2 by catalyzing intracellular H2O2 for hypoxia alleviation. This glucose-activated cascade reaction hydrogel spray can efficiently promote diabetic wound healing, which might provide a reliable tool for synergistic reconstruction of the chronic non-healing wounds.