Mesoporous cerium oxide nanoenzyme for Efficacious impeding tumor and metastasis via Conferring resistance to anoikis.

Tumor cells can survive when detached from the extracellular matrix or lose cell-to-cell connections, leading to a phenomenon known as anoikis resistance (AR). AR is closely associated with the metastasis and proliferation of tumor cells, enabling them to disseminate, migrate, and invade after detachment. Here, we have investigated a novel composite nanoenzyme comprising mesoporous silica/nano-cerium oxide (MSN-Ce@SP/PEG). This nanoenzyme exhibited satisfactory catalase (CAT) activity, efficiently converting high levels of H2O2 within tumor cells into O2, effectively alleviating tumor hypoxia. Furthermore, MSN-Ce@SP/PEG nanoenzyme demonstrated high peroxidase (POD) activity, elevating reactive oxygen species (ROS) levels and attenuating AR in hepatocellular carcinoma (HCC) cells. The MSN-Ce@SP/PEG nanoenzyme exhibited satisfactory dual bioactivity in CAT and POD and was significantly enhanced under favorable photothermal conditions. Through the synergistic effects of these capabilities, the nanoenzyme disrupted the epithelial-mesenchymal transition (EMT) process in detached HCC cells, ultimately inhibiting the recurrence and metastasis potential of anoikis-resistant HCC cells. This study represents the first report of a novel nanoenzyme based on mesoporous silica/nano-cerium oxide for treating AR in HCC cells, thereby suppressing HCC recurrence and metastasis. The findings of this work offer a pioneering perspective for the development of innovative strategies to prevent the recurrence and metastasis of HCC.

Multifunctional MnGA Nanozymes for the Treatment of Ulcerative Colitis by Reducing Intestinal Inflammation and Regulating the Intestinal Flora.

In ulcerative colitis (UC), the formation of an inflammatory environment is due to the combined effects of excess production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), overproduction of proinflammatory cytokines, and disruption of immune system function. There are many kinds of traditional drugs for the clinical treatment of UC, but long-term drug use can cause toxic side effects and drug resistance and can also reduce patient compliance and other drawbacks. Hence, in light of the clinical challenges associated with UC, including the limitations of existing treatments, intense adverse reactions and the development of resistance to medications, no novel therapeutic agents that offer effective relief and maintain a high level of biosafety are urgently needed. Although many anti-inflammatory nanomedicines have been developed by researchers, the development of efficient and nontoxic nanomedicines is still a major challenge in clinical medicine. Using the natural product gallic acid and the metal compound manganese chloride, a highly effective and nontoxic multifunctional nanoenzyme was developed for the treatment of UC. Nanozymes can effectively eliminate ROS and RNS to reduce the inflammation of intestinal epithelial cells caused by oxidation, facilitate the restoration of the intestinal epithelial barrier through the upregulation of tight junction protein expression, and balance the intestinal microbiota to maintain the stability of the intestinal environment. Using a rodent model designed to mimic UC, we monitored body weight, colon length, the spleen index, and the degree of tissue damage and demonstrated that manganese gallate (MnGA) nanoparticles can reduce intestinal inflammation by clearing ROS and active nitrogen. Intestinal flora sequencing revealed that MnGA nanoparticles could regulate the intestinal flora, promote the growth of beneficial bacteria and decrease the levels of detrimental bacteria within the intestinal tract in a mouse model of UC. Thus, MnGA nanoparticles can maintain the balance of the intestinal flora. This study demonstrated that MnGA nanoparticles are excellent antioxidant and effective anti-inflammatory agents, have good biosafety, and can effectively treat UC.

Tumor Microenvironment Cascade Activated Biodegradable Nano-Enzymes for Glutathione-Depletion and Ultrasound-Enhanced Chemodynamic Therapy.

Chemodynamic therapy (CDT) is emerged as a novel and promising tumor therapy by using the powerful reactive oxygen species (ROS) to kill cancer cells. However, the current CDT is remarkably inhibited due to insufficient H2O2 supply and over-expression of glutathione (GSH) in the tumor microenvironment (TME). Herein, a biodegradable self-supplying H2O2 nano-enzyme of CuO2@CaP with a GSH-consumption effect is designed for cascade enhanced CDT to overcome the problem of H2O2 deficiency and GSH overexpression. In this design, CuO2@CaP is gradually degraded to Ca2+, Cu2+, and H2O2 in acidic TME, resulting in synergistically enhanced CDT owing to the efficient self-supplied H2O2 and GSH-depletion and Ca2+ overload therapy. Interestingly, the faster degradation of CuO2@CaP and promoted production rate of •OH are further achieved after triggering with ultrasound (US). And, the US-enhanced CDT and Ca2+ overload synergistic antitumor therapy is successfully achieved in vivo. These findings provide a promising strategy for designing biodegradable nano-enzymes with self-supplying H2O2 and GSH consumption for US-mediated CDT.

RVG-peptide-camouflaged iron-coordinated engineered polydopamine nanoenzyme with ROS scavenging and inhibiting inflammatory response for ischemic stroke therapy.

Stroke is one of the most common causes of death and disability. In addition, most neuroprotective agents fail to rescue neurons from cerebral ischemic insults due to their poor ability to penetrate the blood-brain barrier (BBB). Here, the tailored engineered nanoenzyme has been successfully synthesized by coordination-driven co-assembly of dopamine (DA) and iron ion (Fe3+), which is subsequently camouflaged by neuron-specific rabies viral glycoprotein (RVG) peptide to scavenge reactive oxygen species (ROS) and inhibit inflammatory response in damaged neuron for the efficient therapy of ischemic stroke. The resulting nanoenzyme with good biocompatibility, core-shell structure, and suitable diameter can nondestructively cross the BBB and then internalize into the damaged neuron through the camouflaging and homologous targeted strategy of neuron-specific RVG peptide. After intravenous injection into transient middle cerebral artery occlusion (tMCAO) mouse models, nanoenzyme exerted a significant neuroprotective effect, resulting in a 50 % reduction in neurological scores and an approximate 33 % decrease in cerebral infarction volume. Interestingly, such nanoenzyme can eliminate free radicals, reduce neuroinflammation, enhance BBB integrity, improve mitochondrial function, and inhibit neuronal ferroptosis. Taken together, this well-designed nanoenzyme with its excellent biocompatibility and well-understood mechanisms holds promise a robust therapy for ischemic stroke.

Targeted regulation of autophagy using sorafenib-loaded biomineralization nanoenzyme for enhanced photodynamic therapy of hepatoma.

Sorafenib (SF), a multi-targeted tyrosine kinase inhibitor, serves as a primary therapeutic modality for advanced liver cancer. Nonetheless, its clinical efficacy is hindered by various obstacles, such as limited bioavailability and inadequate accumulation. This study introduces a novel biomimetic mineralization enzyme, known as BSA@Pt/Ce6/SF@M (PCFM). The PCFM incorporates platinum (Pt) as a catalytic agent, SF as a molecular-targeted therapeutic agent, and Ce6 as a photosensitizer within liver cancer cell membranes. This strategy enables the combination of various anti-tumor treatments, such as photodynamic therapy (PDT) and autophagy induction, leading to increased bioavailability of SF and achieving a multidimensional synergistic anticancer effect. The PDT effect produced by Ce6 in PCFM greatly enhances SF-induced autophagy, effectively promoting autophagic cell death. Furthermore, Pt dissociates from the biomineralization process, acquiring peroxidase properties through chemokinetic reactions. This facilitates the catalysis of significant oxygen generation, addressing the challenge of hypoxia in the tumor microenvironment and improving the efficacy of PDT. Moreover, the SF further enhances therapeutic efficacy by inducing autophagy in response to energy deprivation, as indicated by the reduced levels of HIF-1α, p62, along with increased levels of ROS and LC3-Ⅱ/Ι. This biomineralization-based nanoenzyme exhibits strong anti-tumor characteristics, offering a novel strategy for overcoming challenges in liver cancer treatment.

Using Hybrid MnO2-Au Nanoflowers to Accelerate ROS Scavenging and Wound Healing in Diabetes.

Objectives: Excessive reactive oxygen species (ROS) in diabetic wounds are major contributors to chronic wounds and impaired healing, posing significant challenges in regenerative medicine. Developing innovative drug delivery systems is crucial to address these issues by modifying the adverse microenvironment and promoting effective wound healing. Methods: Herein, we designed a novel drug delivery platform using manganese dioxide nanoflower hybridized gold nanoparticle composites (MnO2-Au) synthesized via a hydrothermal reaction, and investigated the potential of MnO2-Au nanoflowers to relieve the high oxidative stress microenvironment and regulate diabetic wound tissue healing. Results: This hybrid material demonstrated superior catalytic activity compared to MnO2 alone, enabling the rapid decomposition of hydrogen peroxide and a substantial reduction in ROS levels within dermal fibroblasts. The MnO2-Au nanoflowers also facilitated enhanced dermal fibroblast migration and Col-I expression, which are critical for tissue regeneration. Additionally, a hydrogel-based wound dressing incorporating MnO2-Au nanoflowers was developed, showing its potential as an intelligent drug delivery system. This dressing significantly reduced oxidative stress, accelerated wound closure, and improved the quality of neonatal epithelial tissue regeneration in a diabetic rat skin defect model. Conclusions: Our findings underscore the potential of MnO2-Au nanoflower-based drug delivery systems as a promising therapeutic approach for chronic wound healing, particularly in regenerative medicine.

Salvaging myocardial infarction with nanoenzyme-loaded hydrogels: Targeted scavenging of mitochondrial reactive oxygen species.

Myocardial infarction resulting from coronary artery atherosclerosis is the leading cause of heart failure, which represents a significant global health burden. The limitations of conventional pharmacologic thrombolysis and flow reperfusion procedures highlight the urgent need for new therapeutic strategies to effectively treat myocardial infarction. In this study, we present a novel biomimetic approach that integrates polyphenols and metal nanoenzymes, inspired by the structure of pomegranates. We developed tannic acid-coated Mn-Co3O4 (MCT) nanoparticles in combination with an injectable collagen hydrogel for the effective treatment of myocardial infarction. The hydrogel enhanced the infarct microenvironment, while the slow-released MCT targets mitochondria to inhibit the post-infarction surge of reactive oxygen species, providing anti-apoptotic and anti-inflammatory effects. RNA sequencing revealed the potential of hydrogels to serve as an interventional mechanism during the post-infarction inflammatory phase. Notably, we found that the hydrogel, when combined with the nanopomegranate-based therapy, significantly improves adverse ventricular remodeling and restores cardiac function in early infarction management. The MCT hydrogel leverages the unique benefits of both MCT nanopomegranates and collagen, demonstrating a synergistic effect. This approach provides a promising example of the potential cooperation between nanomimetic structures and natural biomaterials in therapeutic applications.

An aptasensor with colorimetric and electrochemical dual-outputs for malathion detection utilizing peroxidase-like activity of Fe-MOF.

An aptasensor with dual-outputs was developed for malathion detection. Fe-MOF was synthesized to design favorable signal probes for catalytic amplification. Owing to the excellent peroxidase-like activity of Fe-MOF, the redox reaction was catalyzed to produce the dual-outputs of colorimetric and electrochemical. In this sensing strategy, malathion was captured by the aptamer on sensing interface, leading to the release of signal probe. Thanks to the catalytic amplification of Fe-MOF and the high capture effect of aptamer, the aptasensor produced a sensitive response for malathion. Based on the dual-signals of absorbance and current, the detection method for malathion was developed ranging from 10 ng/mL to 500 ng/mL. The detection limit of malathion was 5.8 ng/mL for colorimetric output and 4.6 ng/mL for electrochemical output. Furthermore, the aptasensor exhibited high specificity and good repeatability in malathion detection. Finally, the aptasensor was applied to detect malathion in fruit and vegetable samples with satisfactory recovery.

Iron-based theranostic nanoenzyme for combined tumor magneto-photo thermotherapy and starvation therapy.

To address the issue of high-dose treatment agents in magnetic hyperthermia-mediated multi-model tumor therapy, a unique iron-based theranostic nanoenzyme with excellent magnetothermal and catalytic properties was constructed. By using a high-temperature arc method, the iron carbon nanoparticles (MF1-3) with a particle size between 13.7 and 27.6 nm and shell thickness between 1 and 5 nm were prepared. After screening, we selected MF3 as the magnetic core due to its high Ms. value and excellent thermal properties. Under the magneto-photo dual thermal conditions, MF3 exhibited a remarkable specific absorption rate (SAR) of 4917 W/g, which was 20 times more than that of iron oxide. Notably, MF3 also exhibited best peroxidase (POD)-like catalytic in pH 5.0 and maintained stable catalytic performance at 45 °C. Considering the "starvation" strategy of cutting off the energy supply to tumor cells and killing them, the glucose oxidase (GOX) and chitosan oligosaccharide (COS) was further grafted onto MF3, forming the MF3/GOX/COS. This multifunctional therapeutic nanoenzyme not only exhibited significant peroxidase-like activity, but also had glucose decomposition and glutathione (GSH) consumption capabilities. The thermal effect significantly promoted the uptake of MF3/GOX/COS by 4T1 cells, and the IC50 value of MF3/GOX/COS reached low to 3.75 µg/mL. In vivo anti-tumor experiment, compared with single treatment methods, the combined therapy of MF3/GOX/COS mediated magneto-photo thermotherapy (M-PTT) and starvation therapy (ST) exhibited higher tumor inhibition rate of 82.1 % by increased cell apoptosis through the mitochondrial pathway. Overall, MF3/GOX/COS therapeutic nanoenzyme combined the advantages of nano-catalysis, M-PTT and ST, providing a solution for achieving sustained, stable, and effective tumor inhibition rates at lower dose levels.

Enteric-coated cerium dioxide nanoparticles for effective inflammatory bowel disease treatment by regulating the redox balance and gut microbiome.

Reactive oxygen species (ROS) play crucial roles in the pathogenesis of inflammatory bowel disease (IBD) by disrupting the mucosal barrier and subsequently leading to the dysregulation of the gut microbiome. Therefore, ROS scavengers present a promising and comprehensive strategy for the effective IBD treatment. In the current work, we explored the therapeutic potential of cerium dioxide (CeO2) nano-enzyme, which is well-known for their potent antioxidant properties and capability to mimic natural antioxidant enzymes in the regulation of oxidative stress. We developed a novel enteric-coated nanomedicine (CeO2@S100) aiming at improving the oral delivery efficacy of CeO2 in the complex gastrointestinal environment. CeO2@S100 is composed of a CeO2 nanoparticle core and a protective polyacrylic acid resin shell (Eudragit S100), ensuring targeted delivery of the core specifically at inflamed intestinal sites due to the negative surface charge. In vivo experiments revealed CeO2@S100 significantly alleviates the IBD by balancing oxidative stress and regulating gut microbiota in a dextran sulfate sodium-induced mouse colitis model. The uncomplicated synthesis of CeO2@S100 highlights its promise for clinical use, presenting an effective and safe approach to managing IBD.

Cobalt ions-derived nanoenzyme array for endosseous neural network reconstruction and osseointegration.

Interactions between bone cells and neurocytes are crucial for endosseous nerve and ensuing bone regeneration. However, absence of neural stem cells in bone makes the innervation of implant osseointegration a major challenge. Herein, a nanorod-like array of sodium hydrogen titanate (ST) co-doped with Co2+ and Co3+, namely STCh that behaves as a reactive oxygen species (ROS)-scavenging enzyme, was hydrothermally formed on Ti substrate. We show that the doped Co2+ and Co3+ locate at TiO6 octahedral interlayers and within octahedra of STCh lattice, appearing releasable and un-releasable, respectively, leading to an increase in Co3+/Co2+ ratio and enzyme activity of the array with immersion. The nanoenzyme-released Co2+ triggers macrophages (MΦs) towards M1 phenotype, then the nanoenzyme scavenges extracellular ROS inducing M1-to-M2 transition. The neurogenic factors secreted by STCh-regulated MΦs, in combination with the released Co2+, promote mesenchymal stem cells to differentiate into neurons and Schwann cells compared to sole Co2+and ST. STCh array greatly enhances nerve reconstruction, type-H capillary formation and ensuing osseointegration in normal rat bone, and antibacteria via engulfing S. aureus by MΦs and osteogenesis in infective case. This nanoenzyme provides an alternative strategy to orchestrate endosseous nerve regeneration for osseointegration without loading exogenous neurotrophins in implants.

Colorimetric aptasensor for Listeria monocytogenes detection using dual functional Fe3O4@MIL-100(Fe) with magnetic separation and oxidase-like activities in food samples.

A novel colorimetric aptasensor assay based on the excellent magnetic responsiveness and oxidase-like activity of Fe3O4@MIL-100(Fe) was developed. Fe3O4@MIL-100(Fe) absorbed with aptamer and blocked by BSA served as capture probe for selective isolation and enrichment of Listeria monocytogenes one of the most common and dangerous foodborne pathogenic bacteria. The aptamer absorbed on Fe3O4@MIL-100(Fe) was further used as signal probe that specifically binds with target bacteria conjugation of capture probe for colorimetric detection of Listeria monocytogenes, taking advantages of its oxidase-like activity. The linear range of the detection of Listeria monocytogenes was from 102 to 107 CFU mL-1, with the limit of detection as low as 14 CFU mL-1. The approach also showed good feasibility for detection of Listeria monocytogenes in milk and meat samples. The spiked recoveries were in the range 81-114% with relative standard deviations ranging from 1.28 to 5.19%. Thus, this work provides an efficient, convenient, and practical tool for selective isolation and colorimetric detection of Listeria monocytogenes in food.

Multifunctional human serum albumin-crosslinked and self-assembling nanoparticles for therapy of periodontitis by anti-oxidation, anti-inflammation and osteogenesis.

Periodontitis is a chronic inflammatory disease that can result in the irreversible loss of tooth-supporting tissues and elevate the likelihood and intensity of systemic diseases. The presence of reactive oxygen species (ROS) and associated related oxidative stress is intricately linked to the progression and severity of periodontal inflammation. Targeted removal of local ROS may serve to attenuate inflammation, improve the unfavorable periodontal microenvironment and potentially reverse ensuing pathological cascades. These ROS scavenging nanoparticles, which possess additional characteristics such as anti-inflammation and osteogenic differentiation, are highly sought after for the treatment of periodontitis. In this study, negative charged human serum albumin-crosslinked manganese-doped self-assembling Prussian blue nanoparticles (HSA-MDSPB NPs) were fabricated. These nanoparticles demonstrate the ability to scavenge multiple ROS including superoxide anion, free hydroxyl radicals, singlet oxygen and hydrogen peroxide. Additionally, HSA-MDSPB NPs exhibit the capacity to alleviate inflammation in gingiva and alveolar bone both in vitro and in vivo. Furthermore, HSA-MDSPB NPs have been shown to play a role in promoting the polarization of macrophages from the M1 to M2 phenotype, resulting in reduced production of pro-inflammatory cytokines. More attractively, HSA-MDSPB NPs have been demonstrated to enhance cellular osteogenic differentiation. These properties of HSA-MDSPB NPs contribute to decreased inflammation, extracellular matrix degradation and bone loss in periodontal tissue. In conclusion, the multifunctional nature of HSA-MDSPB NPs provides a promising therapeutic approach for the treatment of periodontitis.

Design and synthesis of a novel chiral photoacoustic probe and accurate imaging detection of hydrogen peroxide in vivo.

Nanocatalytic medicine, which aims to accurately target and effectively treat tumors through intratumoral in situ catalytic reactions triggered by tumor-specific environments or markers, is an emerging technology. However, the relative lack of catalytic activity of nanoenzymes in the tumor microenvironment (TME) has hampered their use in biomedical applications. Therefore, it is crucial to develop a highly sensitive probe that specifically responds to the TME or disease markers in the TME for precision diagnosis and treatment of diseases. In this work, a chiral photoacoustic (PA) nanoprobe (D/L-Ce@MoO3) based on the H2O2-catalyzed TME activation reaction was constructed in a one-step method using D-cysteine (D-Cys) or L-cysteine (L-Cys), polymolybdate, and cerium nitrate as raw materials. The designed and synthesized D/L-Ce@MoO3 chiral nanoprobe can perform in situ, non-invasive, and precise imaging of pharmacological acute liver injury. In vivo and in vitro experiments have shown that the D/L-Ce@MoO3 probe had chiral properties, the CD signal decreased upon reaction with H2O2, and the absorption and PA signals increased with increasing H2O2 concentration. This is because of the catalytic reaction between Ce ions doped in the nanoenzyme and the high expression of H2O2 caused by drug-induced liver injury to produce ·OH, which has a strong oxidizing property to kill tumor cells and destroy the Mo-S bond in the probe, thus converting the chiral probe into an achiral polyoxometalate (POM) with PA signal.

Bioinspired Core-shell nanospheres integrated in multi-signal immunochromatographic sensor for high throughput sensitive detection of Bongkrekic acid in food.

Nowadays, notable progress has been achieved in detecting foodborne toxins by employing nanoenzyme-based lateral flow immunoassay (NLFIA) sensors in point-of-care testing (POCT). It continues to be a major challenge to maximize the enzyme-like performance of nanozymes for educe any potential uncertainties in catalytic process. In this study, we employed a facile and efficient self-assembly approach to fabricate nucleoid-shell structured biomimetic nanospheres CuS@Au-Pt (CAP), which demonstrates enhanced brightness of the colorimetric signal, excellent affinity, and excellent peroxidase activity. The integration of CAP with a competitive-assay NLFIA platform enabled sensitive immunochromatographic detection of bongkrekic acid (BA), with LOD as low as 0.66 ng/mL. After signal amplification through enzyme-like reaction, the detection range was extended around 1-fold. Additionally, CAP-NLFIA effectively detected BA with a recovery rate of 80.96-119.36% for real samples. The study proposes using CAP as a signal reporter in a dual-readout LFIA, which can establish a high throughput sensitive detection platform.

Multifunctional nanoenzyme lateral flow immunoassay strip for rapid and ultrasensitive detection of carbofuran in vegetables.

A lateral flow immunoassay strip (LFIAS) is one of the most frequently rapid test technologies for carbofuran (CAR). Nevertheless, the LFIAS has a poor quantitative capability and low sensitivity. And, it also requires often complex sample handling steps, making testing time longer. In this study, Fe3O4 nanoparticles were successively modified with MIL-100(Fe)-based metal-organic framework (MOF) and chloroplatinic acid hexahydrate to obtain a core-shell complex of Fe3O4-MOF-Pt. The complex had a peroxidase-mimicking activity catalytic function that enabled signal amplification and sensitivity enhancement. Upon coupling with carbofuran monoclonal antibody (CAR-mAb), the magnetic separation properties of the probe enabled target-specific enrichment. The LFIAS based on Fe3O4-MOF-Pt nanocomposites could detect CAR in the range of 0.25-50 ng mL-1 with a limit of detection (LOD) of 0.15 ng mL-1, enabling colorimetric and catalytic analysis. In addition, the method showed high specificity and stability for detecting CAR in various vegetables, and recovery rates of the spiked samples were 91.40%-102.40%. In conclusion, this study provided one-stop detection of "target enrichment-visual inspection". While lowering the LOD, it reduced the detection time and improved the detection efficiency. The multifunctional Fe3O4-MOF-Pt nanocomposite provides an idea for the construction of novel multifunctional probes to improve the detection performance of conventional LFIAS.

A Fe2O3/CNx cascade nanoreactor with dual-enzyme-mimetic activities for cancer hypoxia relief to amplify chemo/photodynamic therapy.

Reactive oxygen species (ROS)-mediated therapeutic strategies, including chemodynamic therapy (CDT), photodynamic therapy (PDT), and their combination, are effective for treating cancer. Developing a nanoreactor with combined functions of catalase (CAT) and peroxidase (POD) that can simultaneously convert excess H2O2 in tumors into O2 required for type II PDT and hydroxyl radicals (•OH) for CDT can help achieve combined therapy. Here, we reported on a safe Fe2O3/CNx nanoreactor with dual enzyme simulated activity, in which CNx sheet was the carrier and reducing agent to convert Fe2O3 to Fe2+. After modified by MgO2 and photosensitizer Ce6, MgO2-Fe2O3/CNx-Ce6 (MFCC) platform integrated multiple functions, including photosensitizer delivery, compensated H2O2 continuous supply, relieve of hypoxia, generation of •OH and consumption of GSH into a single formulation. Under 660 nm irradiation for 4 min, MFCC actives more ROS to conduct PDT/CDT, leading to the remarkable reduced survival rate of breast cancer cells to 14 %. Due to the enhanced permeability and retention (EPR) effect, MFCC can retain and accumulate at the tumor site of mice for a longer period that inhibit the expression of tumor angiogenic factors, suppress tumor neovascularization, and suppress the proliferation and growth of tumor cells.

Thermoresponsive and Substrate Self-Cycling Nanoenzyme System for Efficient Tumor Therapy.

Cerium oxide (CeO2-x) performs well in photothermal and catalytic properties due to its abundance of oxygen vacancies. Based on this, we designed a thermosensitive therapeutic nanoplatform to achieve continuous circular drug release in tumor. It can solve the limitation caused by insufficient substrate in the process of tumor treatment. Briefly, CeO2-x and camptothecin (CPT) were wrapped in an agarose hydrogel, which could be melted by the photothermal effect of CeO2-x. At the same time, the local temperature increase provided photothermal treatment, which could induce the apoptosis of tumor cell. After that, CPT was released to damage the DNA in tumor cells to realize chemical treatment. In addition, CPT could active nicotinamide adenine dinucleotide oxidase to react with O2 to increase the intracellular H2O2. After that, the exposed CeO2-x could catalyze H2O2 to generate cytotoxic reactive oxygen species for chemodynamic therapy. More importantly, CeO2-x could catalyze H2O2 to produce O2, which could combine with the catalytic action of CPT to construct a substrate self-cycling nanoenzyme system. Overall, this self-cycling nanoplatform released hypoxia in the tumor microenvironment and built a multimode tumor treatment, which achieved an ideal antitumor affect.

Self-assembly of cascade nanoenzyme glucose oxidase encapsulated in copper benzenedicarboxylate for wearable sweat-glucose colorimetric sensors with smartphone readout.

BACKGROUND: With the advent of personalized medical approaches, precise and tailored treatments are expected to become widely accepted for the prevention and treatment of diabetes. Paper-based colorimetric sensors that function in combination with smartphones have been rapidly developed in recent years because it does not require additional equipment and is inexpensive and easy to perform. In this study, we developed a portable, low-cost, and wearable sweat-glucose detection device for in situ detection. RESULTS: The sensor adopted an integrated biomimetic nanoenzyme of glucose oxidase (GOx) encapsulated in copper 1, 4-benzenedicarboxylate (CuBDC) (GOx@CuBDC) through a biomimetic mineralization process. CuBDC exhibited a peroxide-like effect, cascade catalytic effect with the encapsulated GOx, and increased the enzyme stability. GOx@CuBDC and 3,3,5,5-tetramethylbenzidine were combined to form a hybrid membrane that achieved single-step paper-based glucose detection. SIGNIFICANCE AND NOVELTY: This GOx@CuBDC-based colorimetric glucose sensor was used to quantitatively analyze the sweat-glucose concentration with smartphone readings. The sensor exhibited a good linear relationship over the concentration range of 40-900 µM and a limit of detection of 20.7 µM (S/N = 3). Moreover, the sensor performed well in situ monitoring and in evaluating variations based on the consumption of foods with different glycemic indices. Therefore, the fabricated wearable sweat-glucose sensors exhibited optimal practical application performance.

Anti-tumor therapy through high ROS performance induced by Ag nanoenzyme from boron cluster with halloysite clay nanotubes.

The conventional silver nanoparticles (Ag NPs) are characterized with high loading rate and stacking phenomenon, leading to shedding caused biotoxicity and low catalytic efficiency. This seriously hinders their application in biomedicine. Here, we modified the highly dispersible Ag NPs and Ag single-atoms (SAs) synthesis by combining the halloysite clay nanotubes (HNTs) and dodecahydro-dodecaborate (closo-[B12H12]2-) to increase the biocompatible properties and decrease the loading rate. This novel Ag single-atom nanoenzyme alongside Ag NPs nanoenzyme avoid the elevated-temperature calcination while maintaining the exceptionally high-level efficiency of Ag utilization via the reducibility and coordination stabilization of closo-[B12H12]2- and HNTs. With theoretical calculation and electron paramagnetic resonance, we confirmed that both Ag SAzymes and Ag NPs in HNT@B12H12@Ag nanoenzyme are capable decompose the H2O2 into hydroxyl radical (·OH). For the application, we investigated the catalytic activity in the tumor cells and antitumor effects of HNT@B12H12@Ag nanoenzyme both in vitro and in vivo, and confirmed that it effectively suppressed melanoma growth through ·OH generation, with limited biotoxicity. This study provides a novel Ag nanoenzyme synthesis approach to increase the possibility of its clinical application.