Cellular H2O2 Research Articles

Flexible and Stretchable Photoelectrochemical Sensing toward True-to-Life Monitoring of Hydrogen Peroxide Regulation in Endothelial Mechanotransduction.

Hydrogen peroxide (H2O2) levels play a vital role in redox regulation and maintaining the physiological balance of living cells, especially in cell mechanotransduction. Despite the achievements on strain-induced cellular H2O2 monitoring, the applied voltage for H2O2 electrooxidation possibly gave rise to an abnormal expression and inadequate accuracy, which was still an inescapable concern. Hence, we decorated an interlaced CuO@TiO2 nanowires (NWs) semiconductor meshwork onto a polydimethylsiloxane film-supported gold nanotubes substrate (Au NTs/PDMS) to construct a flexible photoelectrochemical (PEC) sensing platform. Under white light irradiation, CuO@TiO2 NWs synergistically exhibited great stretchability and the PEC platform enabled stable photocurrent responses from the reduction of H2O2 even during mechanical deformation. Moreover, the admirable biocompatibility and an almost negligible open circuit voltage of +0.18 V for the CuO@TiO2 NWs/Au NTs/PDMS sensor guaranteed human umbilical vein endothelial cells (HUVECs) adhesion tightly thereon even under continuous illumination for 30 min. Finally, the as-proposed stretchable PEC sensor achieved sensitive and true-to-life monitoring of transient H2O2 release during HUVECs deformation, in which H2O2 release was positively correlated to mechanical strains. This investigation opens a new shade path on in situ cellular sensing and meanwhile greatly expands the application mode of the PEC approach.

In-situ monitoring of cellular H2O2 within 3D cell clusters using conductive scaffolds

Accurately monitoring H2O2 concentrations in 3D cell clusters is challenging due to limited diffusion and rapid degradation of H2O2 in the culture medium. Despite the incorporation of three-dimensional cell culture approaches, the detection technology has largely remained as a 2D planar system. In this study, we present a versatile approach of 3D electrochemical sensing utilizing carbon nanotubes as conductive scaffolds for in-situ monitoring of H2O2 in cell clusters. These scaffolds enabled direct contact between H2O2 released from cells and the electrodes, thereby improving sensitivity and ensuring biocompatibility for cell aggregates. The scaffolds exhibited electrocatalytic behavior with a limit of detection of 6.7 nM H2O2. Additionally, the electrochemical responses of cell clusters with the scaffolds exhibited significantly higher current compared to clusters without scaffolds when stimulated with model drugs. This study underscores the potential of conductive scaffolds for real-time monitoring of H2O2 released from cell clusters in 3D microenvironments.

The role of reactive oxygen species in regulation of the plasma membrane H+-ATPase activity in Masson pine (Pinus massoniana Lamb.) roots responding to acid stress.

To understand the role of reactive oxygen species (ROS) in regulation of the plasma membrane (PM) H+-ATPase in acid-stressed Masson pine roots, different acidity (pH6.6 as the control, pH5.6 and pH4.6) of simulated acid rain (SAR) added with and without external chemicals (H2O2, enzyme inhibitors and ROS scavenger) was prepared. After 30days of SAR exposure, the plant morphological phenotype attributes, levels of cellular ROS and lipid peroxidation, enzymatic activities of antioxidants, PM nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and PM H+-ATPase activity in pine seedlings were measured. Compared with the control, the growth of pine seedlings exposed to SAR in the presence or absence of H2O2 was well-maintained, but the application of Na3VO4, 1,3-dimethyl-2-thiourea, N, N-dimethylthiourea (DMTU) and diphenyleneiodonium chloride (DPI) caused a substantial growth inhibition. In addition, SAR exposure, SAR with H2O2 treatment, and SAR with Na3VO4 treatment increased the cellular H2O2 content, O2- content and malondialdehyde (MDA) content, while the use of DMTU and DPI lead to relatively low levels. Similarly, the enzymatic activities of antioxidants, PM NADPH oxidase and PM H+-ATPase in acid stressed pine seedlings elevated with the increasing acidity. A significant stimulation of these enzymatic activities obtained from SAR with H2O2 treatment was observed, whereas which decreased obviously with the addition of Na3VO4, DMTU and DPI (P<0.05). Moreover, a positive correlation was found between plant morphological attributes and the PM H+-ATPase activity (P<0.05). Besides, the PM H+-ATPase activity positively correlated with the cellular ROS contents and the enzymatic activities of antioxidants and PM NADPH oxidase (P<0.05). Therefore, the PM H+-ATPase is instrumental in the growth of pine seedlings resisting to acid stress by enhancing its activity. The process involves the signaling transduction of cellular ROS and coordination with PM NADPH oxidase.

Morfologi Bawang Merah (Allium ascalonicum L.) Pada Cekaman Kekeringan Terhadap Aplikasi Asam Salisilat

Shallots are the vegetable crop with the highest production in Indonesia. However, the problem with cultivating shallots is that they are not resistant to environmental stress such as drought. The decrease in soil water content to 60% of available water has caused a drought stress effect on shallot plants. The strategy that can be used to limit the harmful effects of lack of water on shallots is the application of salicylic acid. Salicylic acid plays an important role that enhances plant growth and development under drought stress conditions by reducing cell membrane damage in water-stressed plant leaves by reducing cellular lipid peroxidation and H2O2 accumulation. This research aimed to study the growth, yield and physiological responses of shallots under drought stress conditions with the application of salicylic acid. This research was carried out in the greenhouse of the Faculty of Agriculture, University of North Sumatra, Medan from April to June 2024. This research used a factorial randomized block design with 2 treatment factors. The first factor of antioxidant spraying consisted of 4 levels, namely 0 mM (control), 0.5 mM, 1 mM and 1.5 mM. The second factor was the level of drought stress (percentage of soil water content) which consisted of 3 levels, namely 80%, 60% and 40% FC. The results showed that drought stress decreased plant height, number of leaves, number of tillers, shoot fresh weight, root fresh weight, shoot dry weight, root dry weight. Meanwhile, application of salicylic acid up to 1 mM could increas shoot fresh weight, root fresh weight, shoot dry weight, and root dry weight.

One-Pot Synthesis of Nanoflower-Like Zn2SnS4 as Nanozymes for Highly Sensitive Electrochemical Detection of H2O2 Released by Living Cells.

The sensitive and reliable nanozyme-based sensor enables the detection of low concentrations of H2O2 in biological microenvironments, it has potential applications as an in-situ monitoring platform for cellular H2O2 release. The uniformly dispersed bimetallic sulfide (Zn2SnS4) nanoflowers were synthesized via a one-pot hydrothermal method and the two kinds of metal ions can serve as morphology and structure directing agents for each other in the synthetic process. The nanoparticles were utilized as nanozyme materials to fabricate a novel electrochemical sensor, and it exhibits a distinct electrochemical response towards H2O2 with excellent stability and detection capability (with a minimum detection limit of 1.79 nM (S/N=3)), the excellent characteristics facilitate the precise detection of low concentrations of H2O2 in biological microenvironments. Use the macrophages differentiated from leukemia THP-1 cells as a representative sensing model, the sensor was successfully utilized for real-time monitoring of the release of H2O2 induced by living cells, which has significant potential applications in clinical diagnosis and cancer treatment.

Specificity and dynamics of H2O2 detoxification by the cytosolic redox regulatory network as revealed by in vitro reconstitution

The thiol redox state is a decisive functional characteristic of proteins in cell biology. Plasmatic cell compartments maintain a thiol-based redox regulatory network linked to the glutathione/glutathione disulfide couple (GSH/GSSG) and the NAD(P)H system. The basic network constituents are known and in vivo cell imaging with gene-encoded probes have revealed insight into the dynamics of the [GSH]2/[GSSG] redox potential, cellular H2O2 and NAD(P)H+H+ amounts in dependence on metabolic and environmental cues. Less understood is the contribution and interaction of the network components, also because of compensatory reactions in genetic approaches. Reconstituting the cytosolic network of Arabidopsis thaliana in vitro from fifteen recombinant proteins at in vivo concentrations, namely glutathione peroxidase-like (GPXL), peroxiredoxins (PRX), glutaredoxins (GRX), thioredoxins, NADPH-dependent thioredoxin reductase A and glutathione reductase and applying Grx1-roGFP2 or roGFP2-Orp1 as dynamic sensors, allowed for monitoring the response to a single H2O2 pulse. The major change in thiol oxidation as quantified by mass spectrometry-based proteomics occurred in relevant peptides of GPXL, and to a lesser extent of PRX, while other Cys-containing peptides only showed small changes in their redox state and protection. Titration of ascorbate peroxidase (APX) into the system together with dehydroascorbate reductase lowered the oxidation of the fluorescent sensors in the network but was unable to suppress it. The results demonstrate the power of the network to detoxify H2O2, the partially independent branches of electron flow with significance for specific cell signaling and the importance of APX to modulate the signaling without suppressing it and shifting the burden to glutathione oxidation.

Maize catalases are recruited by a virus to modulate viral multiplication and infection.

Given the detrimental effects of excessive reactive oxygen species (ROS) accumulation in plant cells, various antioxidant mechanisms have evolved to maintain cellular redox homeostasis, encompassing both enzymatic components (e.g., catalase, superoxide dismutase) and non-enzymatic ones. Despite extensive research on the role of antioxidant systems in plant physiology and responses to abiotic stresses, the potential exploitation of antioxidant enzymes by plant viruses to facilitate viral infection remains insufficiently addressed. Herein, we demonstrate that maize catalases (ZmCATs) exhibited up-regulated enzymatic activities upon sugarcane mosaic virus (SCMV) infection. ZmCATs played crucial roles in SCMV multiplication and infection by catalysing the decomposition of excess cellular H2 O2 and promoting the accumulation of viral replication-related cylindrical inclusion (CI) protein through interaction. Peroxisome-localized ZmCATs were found to be distributed around SCMV replication vesicles in Nicotiana benthamiana leaves. Additionally, the helper component-protease (HC-Pro) of SCMV interacted with ZmCATs and enhanced catalase activities to promote viral accumulation. This study unveils a significant involvement of maize catalases in modulating SCMV multiplication and infection through interaction with two viral factors, thereby enhancing our understanding regarding viral strategies for manipulating host antioxidant mechanisms towards robust viral accumulation.

Using the heme peroxidase APEX2 to probe intracellular H2O2 flux and diffusion

Currently available genetically encoded H2O2 probes report on the thiol redox state of the probe, which means that they reflect the balance between probe thiol oxidation and reduction. Here we introduce the use of the engineered heme peroxidase APEX2 as a thiol-independent chemogenetic H2O2 probe that directly and irreversibly converts H2O2 molecules into either fluorescent or luminescent signals. We demonstrate sensitivity, specificity, and the ability to quantitate endogenous H2O2 turnover. We show how the probe can be used to detect changes in endogenous H2O2 generation and to assess the roles and relative contributions of endogenous H2O2 scavengers. Furthermore, APEX2 can be used to study H2O2 diffusion inside the cytosol. Finally, APEX2 reveals the impact of commonly used alkylating agents and cell lysis protocols on cellular H2O2 generation.

A Single-Atom Manganese Nanozyme Mn-N/C Promotes Anti-Tumor Immune Response via Eliciting Type I Interferon Signaling.

Tumor microenvironment (TME)-induced nanocatalytic therapy is a promising strategy for cancer treatment, but the low catalytic efficiency limits its therapeutic efficacy. Single-atom catalysts (SACs) are a new type of nanozyme with incredible catalytic efficiency. Here, a single-atom manganese (Mn)-N/C nanozyme is constructed. Mn-N/C catalyzes the conversion of cellular H2O2 to ∙OH through a Fenton-like reaction and enables the sufficient generation of reactive oxygen species (ROS), which induces immunogenic cell death (ICD) of tumor cells and significantly promotes CD8+T anti-tumor immunity. Moreover, RNA sequencing analysis reveals that Mn-N/C treatment activates type I interferon (IFN) signaling, which is critical for Mn-N/C-mediated anti-tumor immune response. Mechanistically, the release of cytosolic DNA and Mn2+ triggered by Mn-N/C collectively activates the cGAS-STING pathway, subsequently stimulating type I IFN induction. A highly efficient single-atom nanozyme, Mn-N/C, which enhances anti-tumor immune response and exhibits synergistic therapeutic effects when combined with the anti-PD-L1 blockade, is proposed.

Combination of High-Dose Parenteral Ascorbate (Vitamin C) and Alpha-Lipoic Acid Failed to Enhance Tumor-Inhibitory Effect But Increased Toxicity in Preclinical Cancer Models.

Intravenous vitamin C (IVC, ascorbate [Asc]) and alpha-lipoic acid (ALA) are frequently coadministered in integrative oncology clinics, with limited understanding of combination effects or drug-drug interactions. As high-dose IVC has anticancer activity through peroxide (H2O2), it is hypothesized that IV ALA, a thiol antioxidant, might have untoward effects when combined with IVC. In vitro combination index (CI) was investigated in 6 types of human cancer cells, using clinically relevant concentrations of Asc (0.625-20 mM) and ALA (0.25, 0.5, and 1 mM) evaluated by nonconstant ratio metrics. Cellular H2O2 was measured using HeLa cells expressing a fluorescent probe HyPer. Mouse xenografts of the metastatic breast cancer MDA-MB-231 were treated with intraperitoneal injections of ALA (10, 20, and 50 mg/kg) and Asc (0.2, 0.5, and 4 g/kg) at various dose levels. Cancer cell lines were sensitive to Asc treatment but not to ALA. There is no evidence ALA becomes a prooxidant at higher doses. The CIs showed a mixture of synergistic and antagonistic effects with different ALA and Asc combination ratios, with a "U" shape response to Asc concentrations. The ALA concentrations did not influence the CIs or cellular H2O2 formation. Adding ALA to Asc dampened the increase of H2O2. Toxicity was observed in mice receiving prolonged treatment of ALA at all doses. The Asc at all doses was nontoxic. The combination of ALA and Asc increased toxicity. The ALA at all doses did not inhibit tumor growth. The Asc at 4 g/kg inhibited tumor growth. Adding ALA 50 mg/kg to Asc 4 g/kg did not enhance the effect, but lower doses of ALA (10 or 20 mg/kg) dampened the inhibitory effect of Asc. These data do not support the concurrent or relative concurrent use of high-dose intravenous ALA with prooxidative high-dose IVC in clinical oncology care with potentially increased toxicity.

Hydrogel design to overcome thermal resistance and ROS detoxification in photothermal and photodynamic therapy of cancer

Responsive heat resistance (by heat shock protein upregulation) and spontaneous reactive oxygen species (ROS) detoxification have been regarded as the major obstacles for photothermal/photodynamic therapy of cancer. To overcome the thermal resistance and improve ROS susceptibility in breast cancer therapy, Au ion-crosslinked hydrogels including indocyanine green (ICG) and polyphenol are devised. Au ion has been introduced for gel crosslinking (by catechol-Au3+ coordination), cellular glutathione depletion, and O2 production from cellular H2O2. ICG can generate singlet oxygen from O2 (for photodynamic therapy) and induce hyperthermia (for photothermal therapy) under the near-infrared laser exposure. (−)-Epigallocatechin gallate downregulates heat shock protein to overcome heat resistance during hyperthermia and exerts multiple anticancer functions in spite of its ironical antioxidant features. Those molecules are concinnously engaged in the hydrogel structure to offer fast gel transformation, syringe injection, self-restoration, and rheological tuning for augmented photo/chemotherapy of cancer. Intratumoral injection of multifunctional hydrogel efficiently suppressed the growth of primary breast cancer and completely eliminated the residual tumor mass. Proposed hydrogel system can be applied to tumor size reduction prior to surgery of breast cancer and the complete remission after its surgery.

Smart Ratiometric SERS Nanoprobe for Real-Time Monitoring Hydrogen Peroxide in Living Cells during NADH Treatment Associated with Ferroptosis.

Studying the oxidative stress, especially the reactive oxygen species (ROS) response of ferroptosis, is crucial for the diagnosis and treatment of cancer based on ferroptosis. However, reliable quantitative analysis of intracellular ROS in cancer treatment for drug screening is still a challenge. Herein, a superior ratiometric SERS nanoprobe was developed for in situ, real-time, and highly sensitive detection of content variation of H2O2 within living cells. The SERS nanoprobe was prepared by coassembly of the internal standard molecule p-mercaptobenzonitrile and the reporter molecule p-mercaptophenylboronic acid on the surface of gold nanoparticles, used for synergistic calibration and detection of H2O2, which enables reliable detection of the true content of intracellular H2O2 without the interference of other substances in cells. Based on the nanoprobe, we found that the level of intracellular H2O2 of cancer cells was increased after the nicotinamide adenine dinucleotide (NADH) treatment, with a dose-dependence to the concentration of NADH. High doses of NADH (above 20 mM) can induce cell death by means of ferroptosis associated with the level elevation of intracellular lipid hydroperoxides. This study highlights the potential of the SERS nanoprobe for tracking content variation of cellular H2O2 and understanding its roles in screening new anticancer drugs.

Catalytic Signal Transduction Theory Enabled Virtual Screening of Nanomaterials for Medical Functions.

ConspectusDeveloping biocompatible catalytic nanomaterials (NMs) to target cancer reactive oxygen species (ROS) has provided an alternative chemotherapy strategy for cancer. Compared to the traditional chemotherapy strategy, this catalytic NM-based strategy can take advantage of the nanoscale and catalytic effects of materials and thus is promising to conquer the troubles from which traditional strategies usually suffer, e.g., high dosage, low targeting, severe toxicity and side effects, and susceptibility to drug resistance. Therefore, the corresponding research has been one of the hottest topics in the frontier interdisciplinary field combining materials, chemistry, biology, and medicine. So far, many NMs have been reported to have potential in cancer catalytic therapy. Despite the progress, the chemicobiological mechanisms and principles, which underlie ROS-targeted catalysis and subsequent cancer therapeutic functions of NMs have remained elusive. Therefore, although numerous inorganic NMs have been synthesized with their structural information deposited in publicly available databases, it is still challenging to computationally design or screen the appropriate candidates with the desired medical functions from the libraries.In this Account, catalytic signal transduction theory has been proposed to bridge the gap between the knowledge of catalytic activities and medical functions of inorganic NMs. The atomistic-level mechanisms responsible for the activities of inorganic NMs in catalyzing cellular ROS conversions, namely, H2O2 activation, H2O2 dismutation, O2 activation, and O2•- dismutation, have been studied by density functional theory calculations. On the basis of the mechanisms, the kinetic equations and prediction models for some of the catalyses have been developed, making it possible to systematically and quantitatively describe the relationships between the surface structures and catalytic activities of NMs. The catalytic signal transduction theory assumes that the catalytic activities of NMs dominate their therapeutic activities in cancer catalytic therapy and that the order of catalytic activities mainly determines the order of therapeutic activities for NMs of the same series. According to this theory, the prediction models have been implemented into computer programs with the aid of machine learning to realize high-throughput computational screening of candidate NMs toward cancer catalytic therapy.The results have revealed mechanisms and rules on how inorganic NMs induce cancer cell death by catalyzing the chemical conversions of cellular ROS. They provided theoretical tools for the in silico design and screening of candidate NMs for cancer therapy. To make catalytic signal transduction a general approach of tuning life with catalytic NMs, the challenge now remains to achieve substrate selectivity for catalytic NMs and a systematic and deep understanding of their interactions with entire biosystems.

Neutralization of TGF-β in combination with IL-6 ameliorates septic arthritis by altering RANKL/OPG interaction in murine lymphocytes

Septic arthritis is an inflammatory joint disease caused by S. aureus. Hematogenous entry of the bacteria to the joint space secretespro-inflammatory cytokines TGF-β and IL-6, which alter the Th17/Treg switch. Inhibition of TGF-β and IL-6 to modulate Th17/Treghomeostasis and RANKL/OPG interaction are not done so far in septic arthritis. Role of lymphocyte-derived TGF-β, IL-10, IL-21 alongwith OPN, OPG, cellular H2O2, SOD and catalase activities, and the expressions of RANKL and MMP2 were studied in total lymphocytesof blood, spleen and synovial tissues of Swiss albino mice treated with antibody against TGF-β along with IL-6 Ab after induction ofseptic arthritis. Simultaneous neutralization of TGF-β along with IL-6 is effective in shifting the Th17 cell into Treg cell of the arthriticmice and modulates RANKL and MMP2 expression that leads to the down-regulation of osteoclastic activity and reduces the production of OPN. Additionally, such treatment reduces oxidative stress via enhancing the activities SOD and catalase enzymes in lymphocytes. So, simultaneous neutralization of TGF-β and IL-6 reduces S. aureus infection-associated inflammatory joint damage by increasing Treg numbers and decreasing the number of pro-inflammatory Th17 cells.

Naked Mole-Rat Cortex Maintains Reactive Oxygen Species Homeostasis During In Vitro Hypoxia or Ischemia and Reperfusion.

Neuronal injury during acute hypoxia, ischemia, and following reperfusion are partially attributable to oxidative damage caused by deleterious fluctuations of reactive oxygen species (ROS). In particular, mitochondrial superoxide (O2•-) production is believed to upsurge during lowoxygen conditions and also following reperfusion, before being dismutated to H2O2 and released into the cell. However, disruptions of redox homeostasis may be beneficially attenuated in the brain of hypoxia-tolerant species, such as the naked mole-rat (NMR, Heterocephalus glaber). As such, we hypothesized that ROS homeostasis is better maintained in the brain of NMRs during severe hypoxic/ ischemic insults and following reperfusion. We predicted that NMR brain would not exhibit substantial fluctuations in ROS during hypoxia or reoxygenation, unlike previous reports from hypoxiaintolerant mouse brain. To test this hypothesis, we measured cortical ROS flux using corrected total cell fluorescence measurements from live brain slices loaded with the MitoSOX red superoxide (O2•-) indicator or chloromethyl 2',7'-dichlorodihydrofluorescein diacetate (CM-H2-DCFDA; which fluoresces with whole-cell hydrogen peroxide (H2O2) production) during various low-oxygen treatments, exogenous oxidative stress, and reperfusion. We found that NMR cortex maintained ROS homeostasis during low-oxygen conditions, while mouse cortex exhibited a ~40% increase and a ~30% decrease in mitochondrial O2•- and cellular H2O2 production, respectively. Mitochondrial ROS homeostasis in NMRs was only disrupted following sodium cyanide application, which was similarly observed in mice. Our results suggest that NMRs have evolved strategies to maintain ROS homeostasis during acute bouts of hypoxia and reoxygenation, potentially as an adaptation to life in an intermittently hypoxic environment.

Copper-Coordinated Covalent Organic Framework Produced a Robust Fenton-Like Effect Inducing Immunogenic Cell Death of Tumors.

Increasing infiltration of CD8+ T cells can enhance the response rate to immune checkpoint blockade (ICB) therapies. In contrast, immunogenic cell death (ICD) induced by intracellular reactive oxygen species (ROS) is an effective strategy to increase CD8+ T cell infiltration. Cuproptosis is newly defined and reported by Tsvetkov etal. A Cu-coordinated covalent organic framework (COF) in which two valence states of copper ions are simultaneously loaded is prepared. On the one hand, Cu2+ undergoes a valence shift generating Cu+ which acts as an effective Fenton-like reagent to catalyze the production of · OH and 1 O2 from cellular overexpressed H2 O2 , causing DNA damage and lipid peroxidation (LPO), which directly produce cytotoxicity. On the other hand, residual Cu2+ can effectively deplete endogenous cellular glutathione (GSH), converting it into glutathione disulfide (GSSG), further increasing intracellular oxidative stress and reducing the scavenging of ROS, thus further enhancing the Fenton-like effect and bringing toxic effects on tumor cells. The synergy of these two functions achieves ICD, helping for transforming "cold tumor" into "hot tumor" and efficient anti-tumor effects eventually. This work provides new insights into coordinated COF and inspire the development of more versatile COF for biomedical applications.

Stretchable Oxygen-Tolerant Sensor Based on a Single-Atom Fe-N4 Electrocatalyst for Observing the Role of Oxidative Stress in Hypertension.

Oxidative stress and related oxidative damage have a causal relation with the pathogenesis of hypertension. Therefore, it is crucial to determine the mechanism of oxidative stress in hypertension by applying mechanical forces on cells to simulate hypertension while monitoring the release of reactive oxygen species (ROS) from cells under an oxidative stress environment. However, cellular level research has rarely been explored because monitoring the ROS released by cells is still challenging owing to the interference of O2. In this study, an Fe single-atom-site catalyst anchored on N-doped carbon-based materials (Fe SASC/N-C) was synthesized, which exhibits excellent electrocatalytic activity for the reduction of hydrogen peroxide (H2O2) at a peak potential of +0.1 V and can effectively avoid the interference of O2. Furthermore, we constructed a flexible and stretchable electrochemical sensor based on the Fe SASC/N-C catalyst to study the release of cellular H2O2 under simulated hypoxic and hypertension conditions. Density functional theory calculations show that the highest transition state energy barrier from the oxygen reduction reaction (ORR), i.e., O2 to H2O, is 0.38 eV. In comparison, the H2O2 reduction reaction (HPRR) can be completed only by overcoming a lower energy barrier of 0.24 eV, endowing the HPRR to be more favorable on Fe SASC/N-C compared with the ORR. This study provided a reliable electrochemical platform for real-time investigation of H2O2-related underlying mechanisms of the hypertension process.

Vanillin Benzothiazole Derivative Reduces Cellular Reactive Oxygen Species and Detects Amyloid Fibrillar Aggregates in Alzheimer's Disease Brain.

The misfolding of amyloid beta (Aβ) peptides into Aβ fibrillary aggregates is a major hallmark of Alzheimer's disease (AD), which responsible for the excess production of hydrogen peroxide (H2O2), a prominent reactive oxygen species (ROS) from the molecular oxygen (O2) by the reduction of the Aβ-Cu(I) complex. The excessive production of H2O2 causes oxidative stress and inflammation in the AD brain. Here, we have designed and developed a dual functionalized molecule VBD by using π-conjugation (C═C) in the backbone structure. In the presence of H2O2, the VBD can turn into fluorescent probe VBD-1 by cleaving of the selective boronate ester group. The fluorescent probe VBD-1 can undergo intramolecular charge transfer transition (ICT) by a π-conjugative system, and as a result, its emission increases from the yellow (532 nm) to red (590 nm) region. The fluorescence intensity of VBD-1 increases by 3.5-fold upon binding with Aβ fibrillary aggregates with a high affinity (Kd = 143 ± 12 nM). Finally, the VBD reduces the cellular toxic H2O2 as proven by the CCA assay and DCFDA assay and the binding affinity of VBD-1 was confirmed by using in vitro histological staining in 8- and 18-month-old triple transgenic AD (3xTg-AD) mice brain slices.

A carbon dot-doped Cu-MOF-based smart nanoplatform for enhanced immune checkpoint blockade therapy and synergistic multimodal cancer therapy.

Immune checkpoint blockade (ICB) is a kind of promising anti-tumor immunotherapy that can block the negative immune regulatory pathways using a particular antibody. Weak immunogenicity in most patients is a key obstacle to ICB therapy. Photodynamic therapy (PDT) is a non-invasive treatment that can enhance the immunogenicity of the host and realize systemic anti-tumor immunotherapy; yet tumor microenvironment hypoxia and glutathione overexpression severely restrict the PDT effect. To overcome the above issues, we design a combination therapy based on PDT and ICB. We prepared red carbon dot (RCD)-doped Cu-metal-organic framework nanoparticles (Cu-MOF@RCD) as smart nano-reactors because their tumor microenvironment and near-infrared light responsive property can decompose tumor endogenous H2O2 through Fenton-like reactions. Cu-MOF@RCD also shows clear near-infrared photothermal therapy (PTT) effect and has an ability to deplete glutathione (DG), which together enhances decomposition of cellular H2O2 and amplifies reactive oxygen species (ROS) levels in cells, thus leading to enhanced PDT and chemodynamic therapy (CDT) effect. Moreover, programmed cell death-ligand 1 antibody (anti-PD-L1) is used together to enable combination therapy, as Cu-MOF@RCD can significantly enhance host immunogenicity. In summary, the combination of Cu-MOF@RCD with anti-PD-L1 antibody exerts a synergistic PDT/PTT/CDT/DG/ICB therapy and can be used to eradicate the primary tumors and inhibit the growth of untreated distant tumors and tumor metastasis.

Catalase-like pleated niobium carbide MXene loaded with polythiophene for oxygenated sonodynamic therapy in solid tumor.

Sonodynamic therapy (SDT), an emerging treatment for solid tumors, has the advantages of deep tissue penetration, non-invasiveness, low side effects, and negligible drug resistance. However, the hypoxic environment of deep solid tumors can discount the efficacy of oxygenated dependent SDT. Here, we synthesized a polythiophene-based sonosensitizer (PT2) and a two-dimensional pleated niobium carbide (Nb2C) Mxene. PT2 was loaded onto the surface of poly(vinylpyrrolidone) (PVP)-coated Nb2C MXene through electrostatic interaction to obtain Nb2C-PVP-PT2 nanosheets (NSs) with a high loading efficiency of 153.7%. Nb2C MXene exhibited catalase-like activity, which could catalyze hydrogen peroxide (H2O2) to produce O2, in turn alleviating tumor hypoxia and enhancing the efficacy of SDT. The depletion of H2O2 further results in abnormal cellular H2O2 levels and reduced tumor cell activity. Moreover, the decomposed NSs led to the release of the sonosensitizer PT2 that can efficiently generate both singlet oxygen and superoxide anions under ultrasound irradiation. These events led to the inhibition of DNA replication of tumor cells, causing tumor cell death, allowing for enhanced SDT efficacy.