Photothermal-Starvation Therapy Nanomodulator Capable of Inhibiting Colorectal Cancer Recurrence and Metastasis by Energy Metabolism Reduction.

The recurrence and metastasis of colorectal cancer (CRC) have been considered as a severe challenge in clinical treatment. Recent studies have demonstrated that matrix metalloproteinases (MMPs) and lactate can promote local tumor angiogenesis, recurrence, and metastasis. The expression of MMPs is highly dependent on energy metabolism, and lactate is considered an alternative energy source for tumor proliferation and metastasis. Therefore, using a rational approach, a photothermal-starvation therapy nanomodulator that can reduce energy metabolism to suppress CRC recurrence and metastasis is designed. To design a suitable nanomodulator, glucose oxidase (GOX), indocyanine green (IR820), and α-cyano-4-hydroxycinnamic acid (CHC) into nanoparticles by a coassembly method are combined. The photothermal properties of IR820 provide the appropriate temperature and oxygen supply for the enzymatic reaction of GOX to promote intracellular glucose consumption. CHC inhibits the expression of monocarboxylate transporter 1 (MCT1), the transporter of lactic acid into cells, and also reduces oxygen consumption and promotes the GOX reaction. Additionally, altering adenosine triphosphate synthesis to block heat shock proteins expression can be an effective means to prevent IR820-mediated photothermal therapy resistance. Thus, this dual photothermal-starvation therapy nanomodulator efficiently suppresses the recurrence and metastasis of CRC by depleting intracellular nutrients.

Biomimetic Yolk-Shell Nanocatalysts for Activatable Dual-Modal-Image-Guided Triple-Augmented Chemodynamic Therapy of Cancer.

Fenton reaction-based chemodynamic therapy (CDT), which applies metal ions to convert less active hydrogen peroxide (H2O2) into more harmful hydroxyl peroxide (·OH) for tumor treatment, has attracted increasing interest recently. However, the CDT is substantially hindered by glutathione (GSH) scavenging effect on ·OH, low intracellular H2O2 level, and low reaction rate, resulting in unsatisfactory efficacy. Here, a cancer cell membrane (CM)-camouflaged Au nanorod core/mesoporous MnO2 shell yolk-shell nanocatalyst embedded with glucose oxidase (GOD) and Dox (denoted as AMGDC) is constructed for synergistic triple-augmented CDT and chemotherapy of tumor under MRI/PAI guidance. Benefiting from the homologous adhesion and immune escaping property of the cancer CM, the nanocatalysts can target tumor and gradually accumulate in tumor site. For triple-augmented CDT, first, the MnO2 shell reacts with intratumoral GSH to generate Mn2+ and glutathione disulfide, which achieves Fenton-like ion delivery and weakening of GSH-mediated scavenging effect, leading to GSH depletion-enhanced CDT. Second, the intratumoral glucose can be oxidized to H2O2 and gluconic acid by GOD, achieving supplementary H2O2-enhanced CDT. Next, the AuNRs absorbing in NIR-II elevate the local tumor temperature upon NIR-II laser irradiation, achieving photothermal-enhanced CDT. Dox is rapidly released for adjuvant chemotherapy due to responsive degradation of MnO2 shell. Moreover, GSH-activated PAI/MRI can be used to monitor CDT process. This study provides a great paradigm for enhancing CDT-mediated antitumor efficacy.

Astaxanthin Inhibits Oxidative Stress-Induced Ku Protein Degradation and Apoptosis in Gastric Epithelial Cells.

Oxidative stress induces DNA damage which can be repaired by DNA repair proteins, such as Ku70/80. Excess reactive oxygen species (ROS) stimulate the activation of caspase-3, which degrades Ku 70/80. Cells with decreased Ku protein levels undergo apoptosis. Astaxanthin exerts antioxidant activity by inducing the expression of catalase, an antioxidant enzyme, in gastric epithelial cells. Therefore, astaxanthin may inhibit oxidative stress-induced DNA damage by preventing Ku protein degradation and thereby suppressing apoptosis. Ku proteins can be degraded via ubiquitination and neddylation which adds ubiquitin-like protein to substrate proteins. We aimed to determine whether oxidative stress decreases Ku70/80 expression through the ubiquitin-proteasome pathway to induce apoptosis and whether astaxanthin inhibits oxidative stress-induced changes in gastric epithelial AGS cells. We induced oxidative stress caused by the treatment of ß-D-glucose (G) and glucose oxidase (GO) in the cells. As a result, the G/GO treatment increased ROS levels, decreased nuclear Ku protein levels and Ku-DNA-binding activity, and induced the ubiquitination of Ku80. G/GO increased the DNA damage marker levels (γ-H2AX; DNA fragmentation) and apoptosis marker annexin V-positive cells and cell death. Astaxanthin inhibited G/GO-induced alterations, including Ku degradation in AGS cells. MLN4924, a neddylation inhibitor, and MG132, a proteasome inhibitor, suppressed G/GO-mediated DNA fragmentation and decreased cell viability. These results indicated that G/GO-induced oxidative stress causes Ku protein loss through the ubiquitin-proteasome pathway, resulting in DNA fragmentation and apoptotic cell death. Astaxanthin inhibited oxidative stress-mediated apoptosis via the reduction of ROS levels and inhibition of Ku protein degradation. In conclusion, dietary astaxanthin supplementation or astaxanthin-rich food consumption may be effective for preventing or delaying oxidative stress-mediated cell damage by suppressing Ku protein loss and apoptosis in gastric epithelial cells.

A Noble AuPtAg-GOx Nanozyme for Synergistic Tumor Immunotherapy Induced by Starvation Therapy-Augmented Mild Photothermal Therapy.

Notwithstanding immune checkpoint blocking (ICB) therapy has made eminent clinical breakthroughs, overcoming immunologically "cold" tumors remains challenging. Here, a cascade potentiated nanomodulator AuPtAg-GOx is engineered for boosting immune responsiveness. Upon 1064 nm laser irradiation, AuPtAg-mediated mild photothermal therapy (PTT) activates cytotoxic T lymphocytes and reverses the immunogenic "cold" tumor microenvironment. Further, to amplify the thermal sensitivity of tumor cells, glucose oxidase (GOx) is introduced to suppress the production of heat shock proteins, thereby promoting mild photothermal therapy. Complementarily, AuPtAg nanozymes with catalase-like activity can ameliorate tumor hypoxia, significantly improving the GOx activity. As a result, the combination of AuPtAg-GOx with self-augmented photothermal ability and PD-L1 antibody can further escalate the antitumor efficacy. The AuPtAg-GOx-based synergistic starvation therapy, mild PTT, and immunotherapy cascade enhancement therapy strategy can be a favorable tool to effectively kill cancer cells.

Antineoplastic Enzyme as Drug Carrier with Activatable Catalytic Activity for Efficient Combined Therapy.

The delivery of glucose oxidase (GOx) requires extra carriers, which suffers from early leakage and exposure of GOx. These issues will be of less concern if GOx itself acts as a drug carrier. However, the catalytic activity of GOx in the blood still needs to be inhibited. Herein, we found that GOx could self-assemble with hydrophobic molecules into uniform and stable nanoparticles (NPs), including sorafenib, 4'-(amino-methyl phenyl)-2,2' : 6',2''-terpyridine modified cyanin and paclitaxel. The catalytic activity of GOx in NPs was significantly inhibited due to the binding of small molecules with its hydrophobic pockets. After dissociation in the tumor acidic microenvironment, the enzyme activity of GOx could be largely recovered. This acidity-triggered "OFF-to-ON" process ensured safe intravenous administration of GOx-based NPs. In vivo experiments showed that the combined starvation therapy and ferroptosis/photothermal therapy/chemotherapy effectively inhibited 4T1 breast tumor growth.

Cascade nanozymes based on the "butterfly effect" for enhanced starvation therapy through the regulation of autophagy.

Although tumor starvation therapy has been proven to be an excellent method for tumor therapy, its efficiency may be weakened by autophagy, a self-protection mechanism exerted by tumors under starvation stress. Interestingly, over-activated autophagy not only improves the efficacy of starvation therapy, but also induces autophagic death. Herein, we report cascade nanozymes for enhanced starvation therapy by inducing over-activated autophagy. First, glucose oxidase (GOx) modified metal-organic frameworks (NH2-MIL88, MOF) were constructed (MOF-GOx). After loading with curcumin (Cur), Cur@MOF-GOx was further decorated with tumor-targeting hyaluronic acid (HA) to obtain Cur@MOF-GOx/HA nanozymes. GOx can catalyze glucose into H2O2 and gluconic acid, which not only leads to tumor starvation, but also provides reactants for the Fenton reaction mediated by the MOF to generate hydroxyl radicals (˙OH) for chemo-dynamic therapy. Most importantly, protective autophagy caused by tumor starvation can be over-activated by Cur to convert autophagy from pro-survival to pro-death, realizing augmented anticancer therapy efficacy. With these cascade reactions, the synergistic action of starvation, autophagy and chemo-dynamic therapy was realized. Generally, the introduction of Cur@MOF-GOx/HA into tumor cells leads to a "butterfly effect", which induces enhanced starvation therapy through subsequent autophagic cell death to completely break the self-protective mechanism of cancer cells, and generate ˙OH for chemo-dynamic therapy. Precise design allows for the use of cascade nanozymes to realize efficient cancer treatment and restrain metastasis.

Effects of glucose oxidase and its combination with B. amyloliquefaciens SC06 on intestinal microbiota, immune response and antioxidative capacity in broilers.

Glucose oxidase (GOD) is an aerobic dehydrogenase, which catalyses the oxidation of ß-D-glucose to gluconic acid and hydrogen peroxide. This study aimed to investigate the effects of dietary glucose oxidase and its combined effects with Bacillus amyloliquefaciens SC06 (BaSC06) on the intestinal microbiota, immune function and antioxidant capacity of broilers. One-day-old male Lingnan yellow-feathered broilers (n = 720) were randomly assigned to four treatment groups: Control group (basal diet), Anti group (basal diet supplemented with 200 mg/kg enramycin), GOD group (basal diet supplemented with 75 U/kg GOD), and combination of GOD and BaSC06 (GB) group (GOD diet (75 U/kg) supplemented with 1 × 108 colony-forming units BaSC06/kg feed), with six replicates per group and 30 birds per replicate. The experiment was conducted over 52 days. The results indicated a significant decrease in α-diversity (Observed species, Chao1, PD_whole_tree and Shannon) with GOD treatment, compared with the control group. GB treatment also significantly decreased the Shannon index of cecal microbiota. GOD treatment significantly decreased the α-diversity, whereas GB treatment significantly increased these indices except for the Chao1 index, compared with the Anti group. Compared with the control group, the relative abundance of Bacteroides in the GOD and GB groups was significantly increased, whereas a decrease in Firmicutes was observed. Compared with the Anti group, GOD treatment significantly increased the relative abundances of Bacteroides and Lactobacillales, while GB treatment significantly increased Lactobacillales and decreased Proteobacteria levels. In addition, GOD treatment significantly decreased interleukin-10 and interferon-γ levels, compared with the control group. In contrast, GB treatment significantly downregulated interferon-γ levels and upregulated secretory immunoglobulin A, transforming growth factor-ß and interleukin-2 expression in the jejunal mucosa. GOD treatment significantly decreased transforming growth factor-ß and interleukin-10 levels, whereas GB treatment markedly increased interferon-γ expression in the jejunal mucosa compared with the Anti group. Furthermore, GB treatment significantly increased the total antioxidant capability levels and the total superoxide dismutase (T-SOD) and catalase (CAT) activities compared with the control group. Meanwhile, GOD treatment significantly increased glutathione peroxidase (GSH-Px) activity in the jejunal mucosa. Total superoxide dismutase, GSH-Px and CAT activities in the Anti group were higher than in the GOD and GB groups. The malondialdehyde levels in the control group were the highest among all groups. In conclusion, our results indicated that supplementation with GOD alone and its combination with BaSC06 in diet could increase antioxidant capacity, immune function and improve the intestinal microbiota composition of broilers. Combination treatment with GOD with BaSC06 exerted stronger effects than GOD treatment only.

Biomineralized Cascade Enzyme-Encapsulated ZIF-8 Nanoparticles Combined with Antisense Oligonucleotides for Drug-Resistant Bacteria Treatment.

The unrestrained use of antibiotics accelerates the development of drug-resistant bacteria and leads to an increasing threat to human health. Therefore, there is an urgent need to explore novel and effective strategies for the treatment of bacterial infections. Herein, zeolite imidazole framework-8 (ZIF-8) material was utilized to construct biomineralized nanomaterial (GOx&HRP@ZIF-8/ASO) by encapsulating biological cascade enzymes and combining with antisense oligonucleotides (ASOs), which achieved effective and synergistic antidrug-resistant bacteria therapy. Various in vitro assays confirmed that GOx&HRP@ZIF-8/ASO exhibited excellent antibacterial properties against Escherichia coli, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA) during catalysis of glucose (Glu), especially the minimum inhibitory concentration (MIC) against MRSA was only 16 µg/mL. Compared with simple ZIF-8 (32.85%) and ftsZ ASO (58.65%), GOx&HRP@ZIF-8/ASO+Glu exhibited superb biofilm destruction ability, and the bacteria removal efficiency of the MRSA biofilm could be as high as 88.2%, indicating that the reactive oxygen species (ROS) produced by the cascade enzyme reaction imparted the main synergistic antibacterial capability, and simultaneously, ftsZ ASO significantly enhanced the antibacterial effect by inhibiting the expression of the ftsZ gene. In vivo anti-infection treatment experiments revealed that GOx&HRP@ZIF-8/ASO exhibited the best wound repairing performance and excellent biocompatibility in the presence of Glu. These findings suggested that GOx&HRP@ZIF-8/ASO has favorably realized high-efficiency treatment of MRSA infection and filled the gap in the antibacterial application of biological enzymes.

Preliminary study on alleviation of heat-induced intestinal inflammation through compensatory effects of glucose oxidase.

1. The influence of glucose oxidase (GOD) supplementation on growth, gut inflammation and its compensatory effects in broilers was investigated before and after heat stress.2. Before heat stress, one-day-old broilers were divided into two groups: the control (CON) and GOD (100 g/t complete feed) groups. On d 21, the CON group was equally divided into CON1 and CON2 groups, and heat stress (35°C) was applied to the CON2 and GOD groups for 8 h/day to the end of the study, d 27 of age. The chickens were either killed before heat stress and 2 d after heat stress for the determination of cytokines in the liver and ileum, serum antioxidant enzymes and ileal microbiota. Growth performance was determined before and 7 d after heat stress.3. The GOD decreased Clostridiales and Enterobacteriaceae families of bacteria and increased ileal nuclear factor-κB, interleukin-1ß, and interferon-γ (P < 0.05) before heat stress. The broilers exhibited compensatory effects, including increases in ileal sirtuin-1, heat shock protein 70 expression, liver nuclear factor erythroid 2-related factor 2 content, serum total antioxidant capacity and glutathione peroxidase level (P < 0.05). At 2 d after heat stress, inflammatory factors were increased in both the CON2 and GOD groups, but the levels were lower in the GOD than CON2 (P < 0.05). On d 7 after heat stress, GOS alleviated heat stress induced growth retardation (P < 0.05).4. These data suggested that GOD supplementation in broiler diets before heat stress stimulated intestinal oxidative stress and produced a compensatory response, which prevented a rapid increase in intestinal inflammatory factors and helped to maintain growth performance under heat stress.

Sensitive silica-alumina modified capacitive non-Faradaic glucose sensor for gestational diabetes.

A highly sensitive silica-alumina (Si-Al)-modified capacitive non-Faradaic glucose biosensor was introduced to monitor gestational diabetes. Glucose oxidase (GOx) was attached to the Si-Al electrode surface as the probe through amine-modification followed by glutaraldehyde premixed GOx as aldehyde-amine chemistry. This Si-Al (∼50 nm) modified electrode surface has increased the current flow upon binding of GOx with glucose. Capacitance values were increased by increasing the glucose concentrations. A mean capacitance value was plotted and the detection limit was found as 0.03 mg/mL with the regression coefficient value, R² = 0.9782 [y = 0.8391x + 1.338] on the linear range between 0.03 and 1 mg/mL. Further, a biofouling experiment with fructose and galactose did not increase the capacitance, indicating the specific glucose detection. This Si-Al-modified capacitance sensor detects a lower level of glucose presence and helps in monitoring gestational diabetes.

Dietary glucose oxidase and/or catalase supplementation alleviates intestinal oxidative stress induced by diquat in weaned piglets.

This study investigated the effects of dietary exogenous glucose oxidase (GOD) and/or catalase (CAT) on the intestinal antioxidant capacity and barrier function in piglets under oxidative stress. Sixty pigs assigned randomly to five treatment groups-CON: basal diet; DIQ: basal diet; GOD: basal diet + 40-U GOD/kg diet; CAT: basal diet + 50-U CAT/kg diet; and GC: basal diet + 40-U GOD/kg diet + 50-U CAT/kg diet-were analyzed. On Day 14, the CON group was injected with saline, and the others were treated with diquat. The results showed that in diquat-treated piglets, supplementation of dietary GOD and CAT elevated the superoxide dismutase and CAT activities and attenuated the malondialdehyde level in plasma and intestinal mucosa, enhanced the duodenal villus height and villus height/crypt depth ratio, upregulated ZO-1 mRNA level, and attenuated the apoptosis of the epithelial cells and caspase-3 mRNA level in the intestine. Additionally, the supplementation upregulated mRNA expression of the intestinal NF-E2-related factor 2-regulated genes in diquat-treated piglets. However, GOD combined with CAT could not alleviate oxidative damage better than supplementation of CAT or GOD alone under oxidative stress. Overall, the study provides a potential alternative that could relieve the weaning stress in piglets and help formulate antibiotic-free diets.

Cyclic reactions-mediated self-supply of H2O2 and O2 for cooperative chemodynamic/starvation cancer therapy.

Hydroxyl radical (·OH)-mediated chemodynamic therapy (CDT) and glucose oxidase (GOx)-based starvation therapy (ST) are two emerging antitumor strategies, limited by acid/H2O2 deficiency and tumor hypoxia, respectively. Herein, we developed a liposomal nanoplatform co-delivering Fe(OH)3-doped CaO2 nanocomposites and GOx molecules for synergistic CDT/ST with a complementary effect. Based on Fenton reactions initiated by iron ions, CaO2-supplied H2O2 could not only generate ·OH for H2O2-sufficient CDT, but also produce O2 to promote the catalytic efficiency of GOx under hypoxia. In return, the enhanced ST generated gluconic acid and H2O2, further amplifying CDT. Through in vitro and in vivo experiments, we demonstrated that such a mutually reinforced modality based on the cyclic Fenton/starvation reactions provided a novel and potent anticancer mechanism for the effective treatment of hypoxic cancers.

Identification of the vibrational marker of tyrosine cation radical using ultrafast transient infrared spectroscopy of flavoprotein systems.

Tryptophan and tyrosine radical intermediates play crucial roles in many biological charge transfer processes. Particularly in flavoprotein photochemistry, short-lived reaction intermediates can be studied by the complementary techniques of ultrafast visible and infrared spectroscopy. The spectral properties of tryptophan radical are well established, and the formation of neutral tyrosine radicals has been observed in many biological processes. However, only recently, the formation of a cation tyrosine radical was observed by transient visible spectroscopy in a few systems. Here, we assigned the infrared vibrational markers of the cationic and neutral tyrosine radical at 1483 and 1502 cm-1 (in deuterated buffer), respectively, in a variant of the bacterial methyl transferase TrmFO, and in the native glucose oxidase. In addition, we studied a mutant of AppABLUF blue-light sensor domain from Rhodobacter sphaeroides in which only a direct formation of the neutral radical was observed. Our studies highlight the exquisite sensitivity of transient infrared spectroscopy to low concentrations of specific radicals.

Versatile electrochemical biosensor based on bi-enzyme cascade biocatalysis spatially regulated by DNA architecture.

The regulation of biocatalytic cascades in microenvironments for high performance and extended applications is still challenging. Herein, we develop a rolling circle amplification (RCA)-based one-pot method to prepare the micron-sized DNA flowers (DFs), which achieve the co-encapsulation and spatial regulation of bi-enzyme molecules, glucose oxidase (GOx) and horseradish peroxidase (HRP). In this system, GOx and HRP are integrated into the DFs simultaneously during RCA with the bridging of magnesium between enzyme residues and phosphate backbones on DFs. The cascade of GOx/HRP is regulated with the formation of highly ordered and hydrogen-bonded water environment in the cavity of DFs, resulting in an enhanced cascade catalytic efficiency compared with that in homogeneous solution. Moreover, the high density of DNA scaffold ensures the encapsulation of GOx/HRP with high efficiency. Accordingly, a glucose electrochemical biosensor with amplified signal response is fabricated using the as-prepared GOx/HRP DFs as biosensing interface, realizing sensitive detection of glucose. Further, through designing the complementary sequence of aptamer into the programmable circular template of RCA, the bi-enzyme co-encapsulated DFs are versatilely applied to sensitive and selective detection of cancerous exosomes and thrombin in "signal-on" and "signal-off" modes, respectively, which are further applied to the analysis of complex biological samples successfully. Overall, the encapsulation of multi-enzyme with DFs proposes a promising strategy to regulate the microenvironment of biocatalytic cascades, which hold great potential in biotechnology, bioanalysis and disease diagnosis.

Mitochondria-targeted nanospheres with deep tumor penetration for photo/starvation therapy.

Tumor masses are three-dimensional (3D). The abnormal physiology of solid tumors is a great barrier to anticancer drug delivery, and the development of effective therapeutic strategies for cancer treatment remains highly challenging. In this study, we have rationally designed IR780 and glucose oxidase (GOx) based poly lactic-co-glycolic acid (PLGA) nanospheres, which can not only selectively accumulate in mitochondria, but also penetrate into 3D tumors deeply at the same time, achieving synergistic treatment of phototherapy and enzyme (GOx)-induced starvation therapy under dual-imaging guidance/monitoring. The lipophilic cationic properties of IR780 enable the nanospheres to penetrate into deep tumor tissues, which has been demonstrated by in vitro 3D tumor modeling and in vivo tumor reconstruction. Meanwhile, the inherent structure of IR780 endows the nanospheres with mitochondrial targeting capability. As mitochondria are susceptible to hyperpyrexia and reactive oxygen species (ROS), mitochondria-targeted phototherapy shows more efficient therapeutic performance. Furthermore, the starvation effect of GOx can cut off the nutrition supply to tumor cells, enhancing the energy metabolism disorder of tumor cells after mitochondrial damage induced by phototherapy, further increasing the damage to tumor cells. In addition, the therapeutic process can be guided/monitored by photoacoustic (PA) and fluorescence (FL) dual imaging. Due to the incorporation of multiple modalities, these nanospheres are promising for cancer theranostics.

Parasitic Wasp Mediates Plant Perception of Insect Herbivores.

Microplitis croceipes is a solitary parasitoid that specializes on noctuid larvae of Helicoverpa zea and Heliothis virescens. Both the parasitoid and its hosts are naturally distributed across a large part of North America. When parasitoids deposit their eggs into hosts, venom and polydnaviruses (PDVs) are also injected into the caterpillars, which can suppress host immune responses, thus allowing parasitoid larvae to develop. In addition, PDVs can regulate host oral cues, such as glucose oxidase (GOX). The purpose of this study was to determine if parasitized caterpillars differentially induce plant defenses compared to non-parasitized caterpillars using two different caterpillar host/plant systems. Heliothis virescens caterpillars parasitized by M. croceipes had significantly lower salivary GOX activity than non-parasitized caterpillars, resulting in lower levels of tomato defense responses, which benefited parasitoid performance by increasing the growth rate of parasitized caterpillars. In tobacco plants, parasitized Helicoverpa zea caterpillars had lower GOX activity but induced higher plant defense responses. The higher tobacco defense responses negatively affected parasitoid performance by reducing the growth rate of parasitized caterpillars, causing longer developmental periods, and reduced cocoon mass and survival of parasitoids. These studies demonstrate a species-specific effect in different plant-insect systems. Based on these results, plant perception of insect herbivores can be affected by parasitoids and lead to positive or negative consequences to higher trophic levels depending upon the particular host-plant system.

Photo-controlled liquid metal nanoparticle-enzyme for starvation/photothermal therapy of tumor by win-win cooperation.

Here, a highly cooperative liquid metal nanoparticle-enzyme (LM@GOX) was constructed for combinational starvation/photothermal therapy of tumor. It was found that the enzyme activity of glucose oxidase (GOX) could be strengthened along with the increased temperature within a given range and its optimal activity is around about 43-60 °C. Utilizing the photothermal conversion ability of liquid metal (LM), the GOX catalytic efficiency could be photo-controlled with improved starvation therapeutic efficiency. Furthermore, due to the accelerating blood flow during the photothermal therapy (PTT), the hypoxic situation in tumor tissues could also be relieved, which would contribute to conquering the hypoxia-suppressed GOX catalysis. In the meanwhile, the severe thermo-resistance of tumor cells during PTT process could be overcome by GOX induced decrease of adenosine triphosphate (ATP) and heat shock proteins (HSPs) level, eventually leading to an improved therapeutic effect of PTT. Both in vitro and in vivo studies proved that LM@GOX could significantly inhibit the growth of solid tumor under NIR illumination by a win-win cooperative starvation/photothermal therapy.

Glucose Oxidase-Instructed Multimodal Synergistic Cancer Therapy.

Over the past 3 years, glucose oxidase (GOx) has aroused great research interest in the context of cancer treatment due to its inherent biocompatibility and biodegradability, and its unique catalytic properties against ß-d-glucose. GOx can effectively catalyze the oxidation of glucose into gluconic acid and hydrogen peroxide. This process depletes oxygen levels, resulting in elevated acidity, hypoxia, and oxidative stress in the tumor microenvironment. All of these changes can be readily harnessed to develop a multimodal synergistic cancer therapy by combining GOx with other therapeutic approaches. Herein, the representative studies of GOx-instructed multimodal synergistic cancer therapy are introduced, and their synergistic mechanisms are discussed systematically. The current challenges and future prospects to advance the development of GOx-based nanomedicines in this cutting-edge research area are highlighted.

Applicability and reliability of the glucose oxidase method in assessing α-amylase activity.

Glucose oxidase (GOD) is an enzyme widely used in glucose monitoring systems owing to its high specificity towards glucose. However, in our previous work maltose was found to show significant interaction with GOD and based on this observation, a novel microplate-based method was developed to assess α-amylase inhibitory activity (GOD method). Concerns regarding the interaction of GOD with maltose has limited the widespread use of the GOD method in assessing α-amylase activity. The present paper provides answers to concerns regarding the interaction of GOD with maltose using HPLC studies and application of the GOD method in assessing α-amylase activity. According to the results, the newly developed GOD method can be considered as a well-suited method for the determination of α-amylase activity and as an easy method to do kinetic studies compared to other available methods.

Nanocatalysts-Augmented and Photothermal-Enhanced Tumor-Specific Sequential Nanocatalytic Therapy in Both NIR-I and NIR-II Biowindows.

The tumor microenvironment (TME) has been increasingly recognized as a crucial contributor to tumorigenesis. Based on the unique TME for achieving tumor-specific therapy, here a novel concept of photothermal-enhanced sequential nanocatalytic therapy in both NIR-I and NIR-II biowindows is proposed, which innovatively changes the condition of nanocatalytic Fenton reaction for production of highly efficient hydroxyl radicals (•OH) and consequently suppressing the tumor growth. Evidence suggests that glucose plays a vital role in powering cancer progression. Encouraged by the oxidation of glucose to gluconic acid and H2 O2 by glucose oxidase (GOD), an Fe3 O4 /GOD-functionalized polypyrrole (PPy)-based composite nanocatalyst is constructed to achieve diagnostic imaging-guided, photothermal-enhanced, and TME-specific sequential nanocatalytic tumor therapy. The consumption of intratumoral glucose by GOD leads to the in situ elevation of the H2 O2 level, and the integrated Fe3 O4 component then catalyzes H2 O2 into highly toxic •OH to efficiently induce cancer-cell death. Importantly, the high photothermal-conversion efficiency (66.4% in NIR-II biowindow) of the PPy component elevates the local tumor temperature in both NIR-I and NIR-II biowindows to substaintially accelerate and improve the nanocatalytic disproportionation degree of H2 O2 for enhancing the nanocatalytic-therapeutic efficacy, which successfully achieves a remarkable synergistic anticancer outcome with minimal side effects.