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.

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.

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.

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.

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.

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.

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.

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.

Harnessing cerium-based biomaterials for the treatment of bone diseases.

Bone, an actively metabolic organ, undergoes constant remodeling throughout life. Disturbances in the bone microenvironment can be responsible for pathologically bone diseases such as periodontitis, osteoarthritis, rheumatoid arthritis and osteoporosis. Conventional bone tissue biomaterials are not adequately adapted to complex bone microenvironment. Therefore, there is an urgent clinical need to find an effective strategy to improve the status quo. In recent years, nanotechnology has caused a revolution in biomedicine. Cerium(III, IV) oxide, as an important member of metal oxide nanomaterials, has dual redox properties through reversible binding with oxygen atoms, which continuously cycle between Ce(III) and Ce(IV). Due to its special physicochemical properties, cerium(III, IV) oxide has received widespread attention as a versatile nanomaterial, especially in bone diseases. This review describes the characteristics of bone microenvironment. The enzyme-like properties and biosafety of cerium(III, IV) oxide are also emphasized. Meanwhile, we summarizes controllable synthesis of cerium(III, IV) oxide with different nanostructural morphologies. Following resolution of synthetic principles of cerium(III, IV) oxide, a variety of tailored cerium-based biomaterials have been widely developed, including bioactive glasses, scaffolds, nanomembranes, coatings, and nanocomposites. Furthermore, we highlight the latest advances in cerium-based biomaterials for inflammatory and metabolic bone diseases and bone-related tumors. Tailored cerium-based biomaterials have already demonstrated their value in disease prevention, diagnosis (imaging and biosensors) and treatment. Therefore, it is important to assist in bone disease management by clarifying tailored properties of cerium(III, IV) oxide in order to promote the use of cerium-based biomaterials in the future clinical setting. STATEMENT OF SIGNIFICANCE: In this review, we focused on the promising of cerium-based biomaterials for bone diseases. We reviewed the key role of bone microenvironment in bone diseases and the main biological activities of cerium(III, IV) oxide. By setting different synthesis conditions, cerium(III, IV) oxide nanostructures with different morphologies can be controlled. Meanwhile, tailored cerium-based biomaterials can serve as a versatile toolbox (e.g., bioactive glasses, scaffolds, nanofibrous membranes, coatings, and nanocomposites). Then, the latest research advances based on cerium-based biomaterials for the treatment of bone diseases were also highlighted. Most importantly, we analyzed the perspectives and challenges of cerium-based biomaterials. In future perspectives, this insight has given rise to a cascade of cerium-based biomaterial strategies, including disease prevention, diagnosis (imaging and biosensors) and treatment.

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

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

A smartphone-assisted portable sensing hydrogel modules based on UCNPs and Co3O4 NPs for fluorescence quantitation of hypoxanthine in aquatic products.

Hypoxanthine is a promising index for evaluating the freshness of various aquatic products. Combined the hydrogels containing upconversion nanoparticles (UCNPs), Co3O4 NPs, and N-ethyl-N-(3-sulfopropyl)-3-methylaniline sodium salt/4-amino-antipyrine (TOPS/4-AAP) with a smartphone, a portable sensor was developed for the convenient, sensitive detection of hypoxanthine. With the H2O2 from xanthine oxidase (XOD)-catalyzed reactions of hypoxanthine, the fluorescence of UCNPs was effectively quenched by the purple product produced from the oxidization of TOPS/4-AAP catalyzed by Co3O4 NPs exhibiting peroxidase activity, among which the color change could be transformed into digital signals for quantification of hypoxanthine. The Green value in the RGB analysis of the fluorescence image was negatively proportional to hypoxanthine concentration in the range of 2.5-20 mg/L with a detection limit of 0.69 mg/L and a quantitation limit of 2.30 mg/L. Finally, this sensor was applied for hypoxanthine detection in real aquatic products, showing potential application for freshness evaluation of aquatic products.

Lanthanide coordination polymers@CuO nanoparticles: Enhanced self-cascade nanoenzyme activity and ratiometric fluorescence assay of glutathione.

Tandem enzyme can catalyze some cascade reactions with high efficiency, and some few tandem enzyme-like mimics have been discovered recently. Further improving the catalytic efficiency of tandem nanoenzymes with facile method may undoubtedly promote and broaden their applications in various fields. In this work, cupric oxide nanoparticles (CuO NPs) with dual-functional enzyme mimics were synthesized using the rapid deposition method in advance, which simultaneously combined with lanthanide infinite coordination polymers (Ln ICPs) during the self-assemble of Tb3+, guanine-5'-triphosphate (GTP) and auxiliary ligand terephthalic acid (TA). Excitingly, the obtained Tb-GTP/TA@CuO ICPs, not only displayed obviously enhanced tandem catalytic activity compared with pure CuO NPs, but also provided a versatile ratiometric platform for ultrahigh selective and sensitive detection of glutathione (GSH) under single-wavelength excitation. A good linear relationship between the ratio signal and the GSH concentration was spanning from 0.001 to 20 µM with an impressive detection limit of 0.50 nM. This study opens a new and universal avenue for preparing integrated multifunctional probes by coupling of nanoenzyme catalytic activity with superior luminescent Ln ICPs through facile method.

Glutathione-mediated copper sulfide nanoplatforms with morphological and vacancy-dependent photothermal catalytic activity for multi-model tannic acid assays.

Interface engineering and vacancy engineering play an important role in the surface and electronic structure of nanomaterials. The combination of the two provides a feasible way for the development of efficient photocatalytic materials. Here, we use glutathione (GSH) as a coordination molecule to design a series of CuxS nanomaterials (CuxS-GSH) rich in sulfur vacancies using a simple ultrasonic-assisted method. Interface engineering can induce amorphous structure in the crystal while controlling the formation of porous surfaces of nanomaterials, and the formation of a large number of random orientation bonds further increases the concentration of sulfur vacancies in the crystal structure. This study shows that interface engineering and vacancy engineering can enhance the light absorption ability of CuxS-GSH nanomaterials from the visible to the near-infrared region, improve the efficiency of charge transfer between CuxS groups, and promote the separation and transfer of optoelectronic electron-hole pairs. In addition, a higher specific surface area can produce a large number of active sites, and the synergistic and efficient photothermal conversion efficiency (58.01%) can jointly promote the better photocatalytic performance of CuxS-GSH nanomaterials. Based on the excellent hot carrier generation and photothermal conversion performance of CuxS-GSH under illumination, it exhibits an excellent ability to mediate the production of reactive oxygen species (ROS) through peroxide cleavage and has excellent peroxidase activity. Therefore, CuxS-GSH has been successfully developed as a nanoenzyme platform for detecting tannic acid (TA) content in tea, and convenient and rapid detection of tannic acid is achieved through the construction of a multi-model strategy. This work not only provides a new way to enhance the enzyme-like activity of nanomaterials but also provides a new prospect for the application of interface engineering and vacancy engineering in the field of photochemistry.

Pt,P-codoped carbon nitride nanoenzymes for fluorescence and colorimetric dual-mode detection of cholesterol.

Cholesterol is an important lipid compound found in a variety of foods, and its level in human blood is closely related to human health. Therefore, development of rapid and accurate POCT (point-of-care testing) methods for cholesterol detection is crucial for assessing food quality and early diagnosis of diseases, in particular, in a resource-limited environment. In this study, a smartphone-assisted colorimetric biosensor is constructed based on platinum,phosphorus-codoped carbon nitride (PtCNP2) for the rapid detection of cholesterol. Phosphorus-doped carbon nitride is prepared by thermal annealing of urea and NH4PF6, into which platinum is atomically dispersed by thermal refluxing. The obtained PtCNP2 exhibits an excellent peroxidase-like activity under physiological pH, whereby colorless o-phenylenediamine (OPD) is oxidized to colored 2,3-diaminophenazine (DAP) in the presence of hydrogen peroxide (H2O2), which can be produced during the oxidation of cholesterol by cholesterol oxidase. A smartphone-assisted visual sensing system is then constructed based on the color recognition software, and rapid on-site detection of cholesterol is achieved by reading the RGB values. Meanwhile, the generated DAP shows an apparent fluorescence signal and can realize highly sensitive detection of cholesterol by the change of the fluorescence signal intensity. Such a cholesterol sensor exhibits a wide linear detection range of 0.5-600 µg mL-1 and a low detection limit of 59 ng mL-1. The practicality of the sensor is successfully demonstrated in the rapid detection of cholesterol in serum and food.

Copper-doped Lanthanide Coordination Polymers as Luminescent Nanoenzyme for Ratiometric Sensing of H2O2 and Glutathione.

Design and fabrication of integrated multifunctional probes with intrinsic catalytic and detection abilities is of great importance to simplify the operation in biosensing application with high sensitivity. Herein, dual-emitting lanthanide coordination polymers (Ln-CPs) were facilely prepared by self-assembly of guanine diphosphate (GDP), terephthalic acid (TA), Tb3+ and Cu2+ designated as Tb/Cu-GDP/TA CPs. The doped Cu2+ endowed CPs with obviously enhanced peroxidase mimicking activity compared with free Cu2+. In the presence of H2O2, the probe catalyzed the oxidation of TA generating a new blue fluorescent product, while the fluorescence of Tb3+ decreased simultaneously. Therefore, a new sensitive ratiometric fluorescent sensor for H2O2 has been developed with a good linear range from 0.01 to 300 µM and limit of 1.62 nM. Moreover, the proposed platform could be extended to GSH ratiometric assay in the presence of H2O2, and interestingly, the detection performance could be easily adjusted by adding different concentration of H2O2. This work will facilitate the development of luminescent nanoenzymes based on Ln-CPs to construct the simple ratiomatric sensing platform.

Highly selective colorimetric determination of glutathione based on sandwich-structured nanoenzymes composed of gold nanoparticle-coated molecular imprinted metal-organic frameworks.

A sandwich-structured composite nanoenzyme (NH2-MIL-101(Fe)@Au@MIP) was prepared using molecularly imprinted polymers, metal-organic frameworks, and gold nanoparticles and a highly selective glutathione (GSH) colorimetric sensor was constructed. The inner part of the composite nanoenzymes is a metal-organic framework loaded with gold nanoparticles (AuNPs), NH2-MIL-101(Fe)@Au, which has superior peroxidase-like activity compared with  NH2-MIL-101(Fe). This is due to the surface plasmon resonance effect of AuNPs. GSH can form strong Au-S bonds with AuNPs, which can significantly reduce the enzymatic activity of NH2-MIL-101(Fe)@Au, thereby changing the absorbance at 450 nm of the sensing system. The degree of change in absorbance is correlated with the concentration of GSH. In the outer part, the molecularly imprinted polymer with oxidized glutathione (GSSG) as a dummy template provided specific pores, which significantly improved the selectivity of the sensing system. The sensor showed good GSH sensing performance in the range 1 ~ 50 µM with a lower limit of detection (LOD) of 0.231 µM and good sensing performance in fetal bovine serum, indicating its high potential for clinical diagnostic applications.

Arginine-Nanoenzyme with Timely Angiogenesis for Promoting Diabetic Wound Healing.

The successful treatment of diabetic wounds requires strategies that promote anti-inflammation, angiogenesis, and re-epithelialization of the wound. Excessive oxidative stress in diabetic ulcers (DUs) inhibits cell proliferation and hinders timely vascular formation and macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2, resulting in a persistent inflammatory environment and a nonhealing wound. We designed arginine-nanoenzyme (FTA) with mimic-catalase and arginine-loading. 2,3,4-trihydroxy benzaldehyde and arginine (Arg) were connected by a Schiff base bond, and the nanoassembly of Arg to FTA was driven by the coordination force between a ferric ion and polyphenol and noncovalent bond force such as a hydrogen bond. FTA could remove excess reactive oxygen species at the wound site in situ and convert it to oxygen to improve hypoxia. Meanwhile, Arg was released and catalytically metabolized by NO synthase in M1 to promote vascular repair in the early phase. In the late phase, the metabolite of Arg catalyzed by arginase in M2 was mainly ornithine, which played a vital role in promoting tissue repair, which implemented angiogenesis timely and prevented hypertrophic scars. Mechanistically, FTA activated the cAMP signaling pathway combined with reducing inflammation and ameliorating angiogenesis, which resulted in excellent therapeutic effects on a DU mice model.

A nanoenzyme-modified hydrogel targets macrophage reprogramming-angiogenesis crosstalk to boost diabetic wound repair.

Diabetic wounds has a gradually increasing incidence and morbidity. Excessive inflammation due to immune imbalance leads to delayed wound healing. Here, we reveal the interconnection between activation of the NLRP3 inflammatory pathway in endotheliocyte and polarization of macrophages via the cGAS-STING pathway in the oxidative microenvironment. To enhance the immune-regulation based on repairing mitochondrial oxidative damage, a zeolitic imidazolate framework-8 coated with cerium dioxide that carries Rhoassociated protein kinase inhibition Y-27632 (CeO2-Y@ZIF-8) is developed. It is encapsulated in a photocross-linkable hydrogel (GelMA) with cationic quaternary ammonium salt groups modified to endow the antibacterial properties (CeO2-Y@ZIF-8@Gel). CeO2 with superoxide dismutase and catalase activities can remove excess reactive oxygen species to limit mitochondrial damage and Y-27632 can repair damaged mitochondrial DNA, thus improving the proliferation of endotheliocyte. After endotheliocyte uptakes CeO2-Y@ZIF-8 NPs to degrade peroxides into water and oxygen in cells and mitochondria, NLRP3 inflammatory pathway is inhibited and the leakage of oxidatively damaged mitochondrial DNA (Ox-mtDNA, a damage-associated molecular pattern) through mPTP decreases. Futhermore, as the cGAS-STING pathway activated by Ox-mtDNA down-regulated, the M2 phenotype polarization and anti-inflammatory factors increase. Collectively, CeO2-Y@ZIF-8@Gel, through remodulating the crosstalk between macrophage reprogramming and angiogenesis to alleviate inflammation in the microenvironment and accelerates wound healing.

Nanoreactor based on single-atom nanoenzymes promotes ferroptosis for cancer immunotherapy.

Immunotherapy is a promising mainstream approach in anti-tumor therapy. It boasts advantages such as durable responses and lower side effects. However, there are still some limitations to be addressed. Current cancer immunotherapy has shown low response rates due to inadequate immunogenicity of certain tumor cells. To address these challenges, an acid-specific nanoreactor was developed, designed to induce immunogenicity by triggering ferroptosis in tumor cells. The nanoreactor integrates glucose oxidase (GOx) with a single-atom nanoenzyme (SAE), which exhibits high peroxidase (POD)-like activity in the acidic tumor microenvironment (TME). This specific acid-sensitivity transforms endogenous hydrogen peroxide (H2O2) into cytotoxic hydroxyl radicals (•OH). GOx enhances the POD-like SAE activity in the nanoreactor by metabolizing glucose in tumor cells, producing gluconic acid and H2O2. This nanoreactor induces high levels of oxidative stress within tumor cells through the synergistic action of SAE and GOx, leading to depletion of GSH and subsequently triggering ferroptosis. The resulting nanoreactor-induced ferroptosis leads to immunogenic cell death (ICD) and significantly recruits T lymphocyte infiltration in tumor tissues. This study was designed with the concept of triggering ferroptosis-dependent ICD mechanism in bladder cancer cells, and developed an acid-specific nanoreactor to enhance the immunotherapy efficacy for bladder cancer, which introduces a novel approach for immunotherapy of bladder cancer.