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New, biocompatible materials with favorable antibacterial activity are highly desirable. In this work, we develop a unique conjugated polymer featuring aggregation‐induced emission (AIE) for reliable bacterial eradication. Thanks to the AIE and donor‐π‐acceptor structure, this polymer shows a high reactive oxygen species (ROS)‐generation ability compared to a low‐mass model compound and the common photosensitizer Chlorin E6. Moreover, the selective binding of pathogenic microorganisms over mammalian cells was found, demonstrating its biocompatibility. The effective growth inhibition of bacteria upon polymer treatment under light irradiation was validated in vitro and in vivo. Notably, the recovery from infection after treatment with our polymer is faster than that with cefalotin. Thus, this polymer holds great promise in fighting against bacteria‐related infections in practical applications. [ABSTRACT FROM AUTHOR]

Cancer cells use elevated glutathione (GSH) levels as an inner line of defense to evade apoptosis and develop drug resistance. In this study, we describe a novel 2,4‐nitrobenzenesulfonyl (DNS) protected 2‐hydroxyisophthalamide system that exploits GSH for its activation into free 2‐hydroxyisophthalamide forming supramolecular M+/Cl− channels. Better permeation of the DNS protected compound into MCF‐7 cells compared to the free 2‐hydroxyisophthalamide and GSH‐activatable ion transport resulted in higher cytotoxicity, which was associated with increased oxidative stress that further reduced the intracellular GSH levels and altered mitochondrial membrane permeability leading to the induction of the intrinsic apoptosis pathway. The GSH‐activatable transport‐mediated cell death was further validated in rat insulinoma cells (INS‐1E); wherein the intracellular GSH levels showed a direct correlation to the resulting cytotoxicity. Lastly, the active compound was found to restrict the growth and proliferation of 3D spheroids of MCF‐7 cells with efficiency similar to that of the anticancer drug doxorubicin. [ABSTRACT FROM AUTHOR]

The superoxide anion (O2.−) is widely engaged in the regulation of cell functions and is thereby intimately associated with the onset and progression of many diseases. To ascertain the pathological roles of O2.− in related diseases, developing effective methods for monitoring O2.− in biological systems is essential. Fluorescence imaging is a powerful tool for monitoring bioactive molecules in cells and in vivo owing to its high sensitivity and high temporal‐spatial resolution. Therefore, increasing numbers of fluorescent imaging probes have been constructed to monitor O2.− inside live cells and small animals. In this minireview, we summarize the methods for design and application of O2.−‐responsive fluorescent probes. Moreover, we present the challenges for detecting O2.− and suggestions for constructing new fluorescent probes that can indicate the production sites and concentration changes in O2.− as well as O2.−‐associated active molecules in living cells and in vivo. [ABSTRACT FROM AUTHOR]

Neutrophils can responsively release reactive oxygen species (ROS) to actively combat infections by exogenous stimulus and cascade enzyme catalyzed bio‐oxidation. A supramolecular nanogel is now used as an artificial neutrophil by enzymatic interfacial self‐assembly of peptides (Fmoc‐Tyr(H2PO3)‐OH) with magnetic nanoparticles (MNPs) and electrostatic loading of chloroperoxidase (CPO). The MNPs within the nanogel can elevate H2O2 levels in cancer cells under programmed alternating magnetic field (AMF) similar to the neutrophil activator, and the loaded CPO within protective peptides nanolayer converts the H2O2 into singlet oxygen (1O2) in a sustained manner for neutrophil‐inspired tumor therapy. As a proof of concept study, both the H2O2 and 1O2 in cancer cells increase stepwise under a programmed alternating magnetic field. An active enzyme dynamic therapy by magnetically stimulated oxygen stress and sustained enzyme bio‐oxidation is thus shown with studies on both cells and animals. [ABSTRACT FROM AUTHOR]

Nanocarriers are employed to deliver photosensitizers for photodynamic therapy (PDT) through the enhanced penetration and retention effect, but disadvantages including the premature leakage and non‐selective release of photosensitizers still exist. Herein, we report a 1O2‐responsive block copolymer (POEGMA‐b‐P(MAA‐co‐VSPpaMA) to enhance PDT via the controllable release of photosensitizers. Once nanoparticles formed by the block copolymer have accumulated in a tumor and have been taken up by cancer cells, pyropheophorbide a (Ppa) could be controllably released by singlet oxygen (1O2) generated by light irradiation, enhancing the photosensitization. This was demonstrated by confocal laser scanning microscopy and in vivo fluorescence imaging. The 1O2‐responsiveness of POEGMA‐b‐P(MAA‐co‐VSPpaMA) block copolymer enabled the realization of self‐amplified photodynamic therapy by the regulation of Ppa release using NIR illumination. This may provide a new insight into the design of precise PDT. [ABSTRACT FROM AUTHOR]

In this study, we successfully synthesized CuxCoyS supraparticles (SPs) on the nanoscale featuring multiple pores inside and strong absorption from 400 to 900 nm. Porous CuxCoyS SPs produced the highest reactive oxygen species (ROS) yield (1.39) when illuminated with near‐infrared (NIR) light. Furthermore, we demonstrated that CuxCoyS SPs could be used to identify cancer cells through intracellular telomerase‐responsive fluorescence (FL) imaging in living cells. Because the CuxCoyS SPs were associated with telomerase‐responsive bioimaging and high ROS production, they can be efficiently used in the diagnosis and therapy of tumors with high selectivity and excellent therapeutic effects in vivo. This study provides a new vision for the creation of multifunctional SPs, which can be used as cellular sensors and control tools for pathologies across a broad range of biological systems. [ABSTRACT FROM AUTHOR]

Nanozymes have emerged as a new generation of antibiotics with exciting broad‐spectrum antimicrobial properties and negligible biotoxicities. However, their antibacterial efficacies are unsatisfactory due to their inability to trap bacteria and their low catalytic activity. Herein, we report nanozymes with rough surfaces and defect‐rich active edges. The rough surface increases bacterial adhesion and the defect‐rich edges exhibit higher intrinsic peroxidase‐like activity compared to pristine nanozymes due to their lower adsorption energies of H2O2 and desorption energy of OH*, as well as the larger exothermic process for the whole reaction. This was demonstrated using drug‐resistant Gram‐negative Escherichia coli and Gram‐positive Staphylococcus aureus in vitro and in vivo. This strategy can be used to engineer nanozymes with enhanced antibacterial function and will pave a new way for the development of alternative antibiotics. [ABSTRACT FROM AUTHOR]

The tunable growth of metal–organic materials has implications for engineering particles and surfaces for diverse applications. Specifically, controlling the self‐assembly of metal–phenolic networks (MPNs), an emerging class of metal–organic materials, is challenging, as previous studies suggest that growth often terminates through kinetic trapping. Herein, kinetic strategies were used to temporally and spatially control MPN growth by promoting self‐correction of the coordinating building blocks through oxidation‐mediated MPN assembly. The formation and growth mechanisms were investigated and used to engineer films with microporous structures and continuous gradients. Moreover, reactive oxygen species generated by ultrasonication expedite oxidation and result in faster (ca. 30 times) film growth than that achieved by other MPN assembly methods. This study expands our understanding of metal–phenolic chemistry towards engineering metal–phenolic materials for various applications. [ABSTRACT FROM AUTHOR]

Heterogenous Fenton‐like reactions are frequently proposed for treating persistent pollutants through the generation of reactive radicals. Despite great efforts to optimize catalyst activity, their broad application in practical settings has been restricted by the low efficiency of hydrogen peroxide or persulfate decomposition as well as ultrafast self‐quenching of the activated radicals. Theoretical calculations predicted that two‐dimensional (2D) metallic 1T phase MoS2 materials with exposed (001) surfaces and (100) edges should have remarkable affinity towards crucial intermediates in the peroxymonosulfate (PMS) activation process. X‐ray photoelectron spectroscopy and in situ Raman spectroscopy were used to show that the exposed metallic Mo sites accelerate the rate‐limiting step of electron transfer. A lamellar membrane made from a stack of 2D MoS2 with tunable interspacing was then designed as the catalyst. The non‐linear transport between the MoS2 nanolayers leads to high water diffusivity so that the short‐lived reactive radicals efficiently oxidize contaminants. [ABSTRACT FROM AUTHOR]

The overproduction of HOCl is highly correlated with diseases such as atherosclerosis, rheumatoid arthritis, and cancer. Whilst acting as a marker of these diseases, HOCl might also be used as an activator of prodrugs or drug delivery systems for the treatment of the corresponding disease. In this work, a new platform of HOCl probes has been developed that integrates detection, imaging, and therapeutic functions. The probes can detect HOCl, using both NIR emission and the naked eye in vitro, with high sensitivity and selectivity at ultralow concentrations (the detection limit is at the nanomolar level). Basal levels of HOCl can be imaged in HL‐60 cells without special stimulation. Moreover, the probes provided by this platform can rapidly release either amino‐ or carboxy‐containing compounds from prodrugs, during HOCl detection and imaging, to realize a therapeutic effect. [ABSTRACT FROM AUTHOR]

Conjugated microporous polymers (CMPs) have full access to the organic synthesis toolbox and feature‐rich functionality, structural diversity, and high surface area. We incorporated ferrocene (Fc) into the backbones of CMPs and systematically engineered their optical energy gaps. Compared with the CMPs without Fc units yet adopting a similar molecular orbital level, Fc‐based CMPs can sufficiently generate reactive oxygen species (ROS) under visible light. The resultant ROS are able to effectively decompose the absorbed pollutants, including organic dyes and chemical warfare agents. Specifically, Fc‐based CMPs significantly outperform commercial TiO2 (P25) in the degradation of methylene blue and are capable of converting 2‐chloroethyl ethyl sulfide (a mustard gas simulant) into a completely nontoxic product. [ABSTRACT FROM AUTHOR]

Abstract: Ionic current rectification (ICR) based nanopipettes allow accurate monitoring of cellular behavior in single living cells. Herein, we proposed a 30 nm nanopipette functionalized with G‐quadruplex DNAzyme as an efficient biomimetic recognizer for ROS generation at subcellular level via the changes of current–voltage relationship. Taking advantages of the ultra‐small tip, the nanopipette could penetrate into a single living cell repeatedly or keep measuring for a long time without compromising the cellular functions. Coupled with precision nanopositioning system, generation of ROS in mitochondria in response to cell inflammation was determined with high spatial resolution. Meanwhile, the changes of aerobic metabolism in different cell lines under drug‐induced oxidative stress were monitored continuously. We believe that the ICR‐nanopipette could be developed as a powerful approach for the study of cellular activities via electrochemical imaging in living cells. [ABSTRACT FROM AUTHOR]

Abstract: Mitochondrial membrane potential is more negative in cancer cells than in normal cells, allowing cancer targeting by delocalized lipophilic cations (DLCs). However, as the difference is rather small, these drugs affect also normal cells. Now a concept of pro‐DLCs is proposed based on an N‐alkylaminoferrocene structure. These prodrugs are activated by the reaction with reactive oxygen species (ROS) forming ferrocenium‐based DLCs. Since ROS are overproduced in cancer, the high‐efficiency cancer‐cell‐specific targeting of mitochondria could be achieved as demonstrated by fluorescence microscopy in combination with two fluorogenic pro‐DLCs in vitro and in vivo. We prepared a conjugate of another pro‐DLC with a clinically approved drug carboplatin and confirmed that its accumulation in mitochondria was higher than that of the free drug. This was reflected in the substantially higher anticancer effect of the conjugate. [ABSTRACT FROM AUTHOR]

Abstract: Hydrogen peroxide (H2O2) has been recognized as one of the most significant ROS (reactive oxygen species) in human health and disease. Because of the intrinsic attributes of H2O2—such as its low reactivity under physiological pH—it is exceedingly challenging to develop small‐molecule fluorescent probes with high selectivity and sensitivity for visualization of H2O2 in an intricate biological milieu. To address this gap, a rationally designed tandem Payne/Dakin reaction is reported that is specific to molecular recognition of H2O2. New H2O2 probes based on this unique chemical strategy can be easily synthesized by a general coupling reaction, and the practical applicability of those probes has been confirmed by the visualization of endogenously produced H2O2 in living cells. In particular, starvation‐induced H2O2 production in mouse macrophages has been detected by the novel probe in both confocal imaging and flow cytometry. This tandem Payne/Dakin reaction provides a basis for developing more sophisticated molecular tools to interrogate H2O2 functions in biological phenomena. [ABSTRACT FROM AUTHOR]

Abstract: Owing to their unique, nanoscale related optical properties, nanostructures assembled from molecular photosensitizers (PSs) have interesting applications in phototheranostics. However, most nanostructured PS assemblies are super‐quenched, thus, preventing their use in photodynamic therapy (PDT). Although some of these materials undergo stimuli‐responsive disassembly, which leads to partial recovery of PDT activity, their therapeutic potentials are unsatisfactory owing to a limited ability to promote generation reactive oxygen species (ROS), especially via type I photoreactions (i.e., not by 1O2 generation). Herein we demonstrate that a new, nanostructured phthalocyanine assembly, NanoPcA, has the ability to promote highly efficient ROS generation via the type I mechanism. The results of antibacterial studies demonstrate that NanoPcA has potential PDT applications. [ABSTRACT FROM AUTHOR]

Abstract: Oxidative stress induced by reactive oxygen species (ROS) is one of the critical factors that involves in the pathogenesis and progression of many diseases. However, lack of proper techniques to scavenge ROS depending on their cellular localization limits a thorough understanding of the pathological effects of ROS. Here, we demonstrate the selective scavenging of mitochondrial, intracellular, and extracellular ROS using three different types of ceria nanoparticles (NPs), and its application to treat Parkinson's disease (PD). Our data show that scavenging intracellular or mitochondrial ROS inhibits the microglial activation and lipid peroxidation, while protecting the tyrosine hydroxylase (TH) in the striata of PD model mice. These results indicate the essential roles of intracellular and mitochondrial ROS in the progression of PD. We anticipate that our ceria NP systems will serve as a useful tool for elucidating the functions of various ROS in diseases. [ABSTRACT FROM AUTHOR]

Abstract: Persulfides (RSSH) have been hypothesized as critical components in sulfur‐mediated redox cycles and as potential signaling compounds, similar to hydrogen sulfide (H2S). Hindering the study of persulfides is a lack of persulfide‐donor compounds with selective triggers that release discrete persulfide species. Reported here is the synthesis and characterization of a ROS‐responsive (ROS=reactive oxygen species), self‐immolative persulfide donor. The donor, termed BDP‐NAC, showed selectivity towards H2O2 over other potential oxidative or nucleophilic triggers, resulting in the sustained release of the persulfide of N‐acetyl cysteine (NAC) over the course of 2 h, as measured by LCMS. Exposure of H9C2 cardiomyocytes to H2O2 revealed that BDP‐NAC mitigated the effects of a highly oxidative environment in a dose‐dependent manner over relevant controls and to a greater degree than common H2S donors sodium sulfide (Na2S) and GYY4137. BDP‐NAC also rescued cells more effectively than a non‐persulfide‐releasing control compound in concert with common H2S donors and thiols. [ABSTRACT FROM AUTHOR]

Abstract: N‐Heterocyclic carbene (NHC) boranes undergo oxidative hydrolysis to give imidazolium salts with excellent kinetic selectivity for HOCl over other reactive oxygen species (ROS), including peroxides and peroxynitrite. Selectivity for HOCl results from the electrophilic oxidation mechanism of NHC boranes, which stands in contrast to the nucleophilic oxidation mechanism of arylboronic acids with ROS. The change in polarity that accompanies the conversion of NHC boranes to imidazolium salts can control the formation of emissive excimers, forming the basis for the design of the first fluorescence probe for ROS based on the oxidation of B−H bonds. Two‐photon microscope (TPM) ratiometric imaging of HOCl in living cells and tissues is demonstrated. [ABSTRACT FROM AUTHOR]

Cancer cells produce elevated levels of reactive oxygen species, which has been used to design cancer specific prodrugs. Their activation relies on at least a bimolecular process, in which a prodrug reacts with ROS. However, at low micromolar concentrations of the prodrugs and ROS, the activation is usually inefficient. Herein, we propose and validate a potentially general approach for solving this intrinsic problem of ROS-dependent prodrugs. In particular, known prodrug 4-( N-ferrocenyl- N-benzylaminocarbonyloxymethyl)phenylboronic acid pinacol ester was converted into its lysosome-specific analogue. Since lysosomes contain a higher concentration of active ROS than the cytoplasm, activation of the prodrug was facilitated with respect to the parent compound. Moreover, it was found to exhibit high anticancer activity in a variety of cancer cell lines (IC50=3.5-7.2 μ m) and in vivo (40 mg kg−1, NK/Ly murine model) but remained weakly toxic towards non-malignant cells (IC50=15-30 μ m). [ABSTRACT FROM AUTHOR]

Nanoelectrodes allow precise and quantitative measurements of important biological processes at the single living-cell level in real time. Cylindrical nanowire electrodes (NWEs) required for intracellular measurements create a great challenge for achieving excellent electrochemical and mechanical performances. Herein, we present a facile and robust solution to this problem based on a unique SiC-core-shell design to produce cylindrical NWEs with superior mechanical toughness provided by the SiC nano-core and an excellent electrochemical performance provided by the ultrathin carbon shell that can be used as such or platinized. The use of such NWEs for biological applications is illustrated by the first quantitative measurements of ROS/RNS in individual phagolysosomes of living macrophages. As the shell material can be varied to meet any specific detection purpose, this work opens up new opportunities to monitor quantitatively biological functions occurring inside cells and their organelles. [ABSTRACT FROM AUTHOR]

The two oxidation states of ceria nanoparticles, Ce3+ and Ce4+, play a pivotal role in scavenging reactive oxygen species (ROS). In particular, Ce3+ is largely responsible for removing O2− and .OH that are associated with inflammatory response and cell death. The synthesis is reported of 2 nm ceria-zirconia nanoparticles (CZ NPs) that possess a higher Ce3+/Ce4+ ratio and faster conversion from Ce4+ to Ce3+ than those exhibited by ceria nanoparticles. The obtained Ce0.7Zr0.3O2 (7CZ) NPs greatly improve ROS scavenging performance, thus regulating inflammatory cells in a very low dose. Moreover, 7CZ NPs are demonstrated to be effective in reducing mortality and systemic inflammation in two representative sepsis models. These findings suggest that 7CZ NPs have the potential as a therapeutic nanomedicine for treating ROS-related inflammatory diseases. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is widely used to treat diverse diseases, but its dependence on oxygen to produce cytotoxic reactive oxygen species (ROS) diminishes the therapeutic effect in a hypoxic environment, such as solid tumors. Herein, we developed a ROS-producing hybrid nanoparticle-based photosensitizer capable of maintaining high levels of ROS under both normoxic and hypoxic conditions. Conjugation of a ruthenium complex (N3) to a TiO2 nanoparticle afforded TiO2-N3. Upon exposure of TiO2-N3 to light, the N3 injected electrons into TiO2 to produce three- and four-fold more hydroxyl radicals and hydrogen peroxide, respectively, than TiO2 at 160 mmHg. TiO2-N3 maintained three-fold higher hydroxyl radicals than TiO2 under hypoxic conditions via N3-facilitated electron-hole reduction of adsorbed water molecules. The incorporation of N3 transformed TiO2 from a dual type I and II PDT agent to a predominantly type I photosensitizer, irrespective of the oxygen content. [ABSTRACT FROM AUTHOR]

Heteroatom doping is an effective way to adjust the fluorescent properties of carbon quantum dots. However, selenium-doped carbon dots have rarely been reported, even though selenium has unique chemical properties such as redox-responsive properties owing to its special electronegativity. Herein, a facile and high-output strategy to fabricate selenium-doped carbon quantum dots (Se-CQDs) with green fluorescence (quantum yield 7.6 %) is developed through the hydrothermal treatment of selenocystine under mild conditions. Selenium heteroatoms endow the Se-CQDs with redox-dependent reversible fluorescence. Furthermore, free radicals such as .OH can be effectively scavenged by the Se-CQDs. Once Se-CQDs are internalized into cells, harmful high levels of reactive oxygen species (ROS) in the cells are decreased. This property makes the Se-CQDs capable of protecting biosystems from oxidative stress. [ABSTRACT FROM AUTHOR]

Ratiometric sensors generally couple binding events or chemical reactions at a distal site to changes in the fluorescence of a core fluorophore scaffold. However, such approaches are often hindered by spectral overlap of the product and reactant species. We provide a strategy to design ratiometric sensors that display dramatic spectral shifts by leveraging the chemoselective reactivity of novel functional groups inserted within fluorophore scaffolds. As a proof-of-principle, fluorophores containing a borinate ( RF620) or silanediol ( SiOH2R) functionality at the bridging position of the xanthene ring system are developed as endogenous H2O2 sensors. Both these fluorophores display far-red to near-infrared excitation and emission prior to reaction. Upon oxidation by H2O2 both sensors are chemically converted to tetramethylrhodamine, producing significant (≥66 nm) blue-shifts in excitation and emission maxima. This work provides a new concept for the development of ratiometric probes. [ABSTRACT FROM AUTHOR]

Angiogenin (ANG) is a human ribonuclease that is compromised in patients with amyotrophic lateral sclerosis (ALS). ANG also promotes neovascularization, and can induce hemorrhage and encourage tumor growth. The causal neurodegeneration of ALS is associated with reactive oxygen species, which are also known to elicit the oxidative cleavage of carbon-boron bonds. We have developed a synthetic boronic acid mask that restrains the ribonucleolytic activity of ANG. The masked ANG does not stimulate endothelial cell proliferation but protects astrocytes from oxidative stress. By differentiating between the two dichotomous biological activities of ANG, this strategy could provide a viable pharmacological approach for the treatment of ALS. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) exhibits promising protective effects in many (patho)physiological processes, as evidenced by recent reports using synthetic H2S donors in different biological models. Herein, we report the design and evaluation of compounds denoted PeroxyTCM, which are the first class of reactive oxygen species (ROS)-triggered H2S donors. These donors are engineered to release carbonyl sulfide (COS) upon activation, which is quickly hydrolyzed to H2S by the ubiquitous enzyme carbonic anhydrase (CA). The donors are stable in aqueous solution and do not release H2S until triggered by ROS, such as hydrogen peroxide (H2O2), superoxide (O2−), and peroxynitrite (ONOO−). We demonstrate ROS-triggered H2S donation in live cells and also demonstrate that PeroxyTCM-1 provides protection against H2O2-induced oxidative damage, suggesting potential future applications of PeroxyTCM and similar scaffolds in H2S-related therapies. [ABSTRACT FROM AUTHOR]

Fluorescence imaging of tyrosinase (a cancer biomarker) in living organisms is of great importance for biological studies. However, selective detection of tyrosinase remains a great challenge because current fluorescent probes that contain the 4-hydroxyphenyl moiety show similar fluorescence responses to both tyrosinase and some reactive oxygen species (ROS), thereby suffering from ROS interference. Herein, a new tyrosinase-recognition 3-hydroxybenzyloxy moiety, which exhibits distinct fluorescence responses for tyrosinase and ROS, is proposed. Using the recognition moiety, we develop a near-infrared fluorescence probe for tyrosinase activity, which effectively eliminates the interference from ROS. The high specificity of the probe was demonstrated by imaging and detecting endogenous tyrosinase activity in live cells and zebrafish and further validated by an enzyme-linked immunosorbent assay. The probe is expected to be useful for the accurate detection of tyrosinase in complex biosystems. [ABSTRACT FROM AUTHOR]

Als Technologie zur elektrochemischen Energiespeicherung mit der höchsten theoretischen Kapazität sind Lithium ‐ Sauerstoff ‐ Batterien mit großen Herausforderungen im Hinblick auf die schlechte Stabilität und den geringen Round ‐ Trip ‐ Wirkungsgrad beim Laden/Entladen verbunden. Es ist allgemein anerkannt, dass diese Probleme mit den parasitären chemischen Reaktionen an der Anode, im Elektrolyten und an der Kathode in Zusammenhang stehen. Während die detaillierten Mechanismen dieser Reaktionen gesondert untersucht wurden, sind die möglichen synergistischen Effekte zwischen ihnen immer noch schlecht verstanden. Um diese Wissenslücke zu schließen, behandelt dieser Kurzaufsatz Literaturberichte zu den parasitären chemischen Reaktionen und stellt als entscheidenden chemischen Vermittler die reaktiven Sauerstoffspezies heraus, die an fast allen parasitären chemischen Reaktionen beteiligt sind oder diese fördern. In Anbetracht des ubiquitären Vorkommens von Sauerstoff in allen Testzellen ist diese Erkenntnis von großer Wichtigkeit. Sie liefert neue Einblicke dazu, wie verschiedene Komponenten von Lithium ‐ Sauerstoff ‐ Batterien für den Hochleistungsbetrieb stabilisiert werden können und wie das Potenzial dieser aussichtsreichen Technologie voll ausgeschöpft werden kann. Ein Rad greift ins andere: In Lithium ‐ Sauerstoff ‐ Batterien sind reaktive Sauerstoffspezies an fast allen parasitären chemischen Reaktionen an der Anode, der Kathode und im Elektrolyten beteiligt oder fördern diese. Das Verständnis ihres synergistischen Effekts wird eine rationalere Entwicklung zukünftiger Lithium ‐ Sauerstoff ‐ Batterien ermöglichen. [ABSTRACT FROM AUTHOR]

Graphitic carbon nitride (g-C3N4) has been used as photosensitizer to generate reactive oxygen species (ROS) for photodynamic therapy (PDT). However, its therapeutic efficiency was far from satisfactory. One of the major obstacles was the overexpression of glutathione (GSH) in cancer cells, which could diminish the amount of generated ROS before their arrival at the target site. Herein, we report that the integration of Cu2+ and g-C3N4 nanosheets (Cu2+-g-C3N4) led to enhanced light-triggered ROS generation as well as the depletion of intracellular GSH levels. Consequently, the ROS generated under light irradiation could be consumed less by reduced GSH, and efficiency was improved. Importantly, redox-active species Cu+-g-C3N4 could catalyze the reduction of molecular oxygen to the superoxide anion or hydrogen peroxide to the hydroxyl radical, both of which facilitated the generation of ROS. This synergy of improved ROS generation and GSH depletion could enhance the efficiency of PDT for cancer therapy. [ABSTRACT FROM AUTHOR]

In this work, for the first time, we constructed a novel multi-nanozymes cooperative platform to mimic intracellular antioxidant enzyme-based defense system. V2O5 nanowire served as a glutathione peroxidase (GPx) mimic while MnO2 nanoparticle was used to mimic superoxide dismutase (SOD) and catalase (CAT). Dopamine was used as a linker to achieve the assembling of the nanomaterials. The obtained V2O5@pDA@MnO2 nanocomposite could serve as one multi-nanozyme model to mimic intracellular antioxidant enzyme-based defense procedure in which, for example SOD, CAT, and GPx co-participate. In addition, through assembling with dopamine, the hybrid nanocomposites provided synergistic antioxidative effect. Importantly, both in vitro and in vivo experiments demonstrated that our biocompatible system exhibited excellent intracellular reactive oxygen species (ROS) removal ability to protect cell components against oxidative stress, showing its potential application in inflammation therapy. [ABSTRACT FROM AUTHOR]

A diradical approach to obtain stable organic dyes with intense absorption around λ=1100 nm is reported. The para- and meta-quinodimethane-bridged BODIPY dimers BD-1 and BD-2 were synthesized and were found to have a small amount of diradical character. These molecules exhibited very intense absorption at λ=1088 nm ( ɛ=6.65×105 M−1 cm−1) and 1136 nm ( ɛ=6.44×105 M−1 cm−1), respectively, together with large two-photon-absorption cross-sections. Structural isomerization induced little variation in their diradical character but distinctive differences in their physical properties. Moreover, the compounds showed a selective fluorescence turn-on response in the presence of the hydroxyl radical but not with other reactive oxygen species. [ABSTRACT FROM AUTHOR]

The breast cancer stem cell (CSC) potency of a series of copper(II)-phenanthroline complexes containing the nonsteroidal anti-inflammatory drug (NSAID), indomethacin, is reported. The most effective copper(II) complex in this series, 4, selectivity kills breast CSC-enriched HMLER-shEcad cells over breast CSC-depleted HMLER cells. Furthermore, 4 reduces the formation, size, and viability of mammospheres, to a greater extent than salinomycin, a potassium ionophore known to selectively inhibit CSCs. Mechanistic studies revealed that the CSC-specificity observed for 4 arises from its ability to generate intracellular reactive oxygen species (ROS) and inhibit cyclooxygenase-2 (COX-2), an enzyme that is overexpressed in breast CSCs. The former induces DNA damage, activates JNK and p38 pathways, and leads to apoptosis. [ABSTRACT FROM AUTHOR]

Recent studies posit that reactive oxygen species (ROS) contribute to the cell lethality of bactericidal antibiotics. However, this conjecture has been challenged and remains controversial. To resolve this controversy, we adopted a strategy that involves DNA polymerase IV (PolIV). The nucleotide pool of the cell gets oxidized by ROS and PolIV incorporates the damaged nucleotides (especially 8oxodGTP) into the genome, which results in death of the bacteria. By using a combination of structural and biochemical tools coupled with growth assays, it was shown that selective perturbation of the 8oxodGTP incorporation activity of PolIV results in considerable enhancement of the survival of bacteria in the presence of the norfloxacin antibiotic. Our studies therefore indicate that ROS induced in bacteria by the presence of antibiotics in the environment contribute significantly to cell lethality. [ABSTRACT FROM AUTHOR]

Oxidative stress is considered as an important factor and an early event in the etiology of Alzheimer's disease (AD). Cu bound to the peptide amyloid-β (Aβ) is found in AD brains, and Cu-Aβ could contribute to this oxidative stress, as it is able to produce in vitro H2O2 and HO' in the presence of oxygen and biological reducing agents such as ascorbate. The mechanism of Cu-Aβ-catalyzed H2O2 production is however not known, although it was proposed that H2O2 is directly formed from O2 via a 2-electron process. Here, we implement an electrochemical setup and use the specificity of superoxide dismutase-1 (SOD1) to show, for the first time, that H2O2 production by Cu-Aβ in the presence of ascorbate occurs mainly via a free O2*1 intermediate. This finding radically changes the view on the catalytic mechanism of H2O2 production by Cu-Aβ, and opens the possibility that Cu-Aβcatalyzed O2*1 contributes to oxidative stress in AD, and hence may be of interest. [ABSTRACT FROM AUTHOR]

Oxidative stress is considered as an important factor and an early event in the etiology of Alzheimer's disease (AD). Cu bound to the peptide amyloid-β (Aβ) is found in AD brains, and Cu-Aβ could contribute to this oxidative stress, as it is able to produce in vitro H2O2 and HO' in the presence of oxygen and biological reducing agents such as ascorbate. The mechanism of Cu-Aβ-catalyzed H2O2 production is however not known, although it was proposed that H2O2 is directly formed from O2 via a 2-electron process. Here, we implement an electrochemical setup and use the specificity of superoxide dismutase-1 (SOD1) to show, for the first time, that H2O2 production by Cu-Aβ in the presence of ascorbate occurs mainly via a free O2*1 intermediate. This finding radically changes the view on the catalytic mechanism of H2O2 production by Cu-Aβ, and opens the possibility that Cu-Aβcatalyzed O2*1 contributes to oxidative stress in AD, and hence may be of interest. [ABSTRACT FROM AUTHOR]

Potentielle biomedizinische Anwendungen von Graphenoxid (GO), z. B. als Träger von Biomolekülen, Reagentien für die photothermische Therapie oder Biosensoren, werden durch die Zytotoxizität und Mutagenität dieses Materials eingeschränkt. Es wird davon ausgegangen, dass diese Eigenschaften zumindest zum Teil auf eine von GO verursachte Erhöhung des oxidativen Stresses in Zellen zurückzuführen ist. Es ist jedoch nicht bekannt, auf welchen chemischen Fragmenten dieser ungünstige Effekt beruht. In dieser Arbeit wurden vier GOs entwickelt, welche verschiedene redoxaktive Gruppen wie Mn2+, C ‐ zentrierte Radikale sowie Endoperoxide (EPs) auf der Oberfläche besitzen. Der Vergleich der Fähigkeit der Materialien, reaktive Sauerstoffspezies in humanen Gebärmutterhalskrebszellen zu generieren, zeigt, dass EPs eine entscheidende Rolle im GO ‐ induzierten oxidativen Stress spielen. Diese Ergebnisse können für die gezielte Entwicklung von biokompatiblem und nicht ‐ toxischem GO für biomedizinische Anwendungen verwendet werden. Auf der Suche nach dem Schuldigen: Die Anwendung von Graphenoxid (GO) in der Biomedizin wird durch dessen Zytotoxizität und Mutagenität eingeschränkt. Um herauszufinden, welche chemischen Fragmente diese Toxizität verursachen, wurden GOs mit verschiedenen redoxaktiven Oberflächengruppen hergestellt und verglichen. Es zeigt sich, dass Endoperoxide entscheidend zur Generierung reaktiver Sauerstoffspezies beitragen. [ABSTRACT FROM AUTHOR]

A sensitive bioluminogenic probe for highly reactive oxygen species (hROS), SO³H-APL, was developed based on the concept of dual control of bioluminescence emission by means of bioluminescent enzyme-induced electron transfer (BioLeT) and modulation of cell-membrane permeability. This probe enables non-invasive visualization of physiologically relevant amounts of hROS generated deep inside the body of living rats for the first time. It is expected to serve as a practical analytical tool for investigating a wide range of biological functions of hROS in vivo. The design concept should be applicable to other in vivo bioluminogenic probes. [ABSTRACT FROM AUTHOR]

Endo/lysosomal escape of gene vectors and the subsequent unpacking of nucleic acids in cytosol are two major challenges for efficient gene delivery. Herein, we report a polymeric gene delivery vector, which consists of a photosensitizer (PS) with aggregation-induced emission (AIE) characteristics and oligoethylenimine (OEI) conjugated via an aminoacrylate (AA) linker that can be cleaved by reactive oxygen species (ROS). In aqueous media, the polymer could self-assemble into bright red fluorescent nanoparticles (NPs), which can efficiently bind to DNA through electrostatic interaction for gene delivery. Upon visible light irradiation, the generated ROS can break the endo/lysosomal membrane and the polymer, resulting in light-controlled endo/lysosomal escape and unpacking of DNA for efficient gene delivery. The smart polymer represents the first successful gene vector to simultaneously address both challenges with a single light excitation process. [ABSTRACT FROM AUTHOR]

Novel isoselenazoles with high glutathione peroxidase (GPx) and peroxiredoxin (Prx) activities provide remarkable cytoprotection to human cells, mainly by exhibiting antioxidant activities in the presence of cellular thiols. The cytotoxicity of the isoselenazoles is found to be significantly lower than that of ebselen, which is being clinically evaluated by several groups for the treatment of reperfusion injuries and stroke, hearing loss, and bipolar disorder. The compounds reported in this paper have the potential to be used as therapeutic agents for disorders mediated by reactive oxygen species. [ABSTRACT FROM AUTHOR]

Multiplex analyte detection in complex dynamic systems is desirable for the investigation of cellular communication networks as well as in medical diagnostics. A family of lanthanide-based responsive luminescent probes for multiplex detection is reported. The high modularity of the probe design enabled the rapid assembly of both green and red emitters for a large variety of analytes by the simple exchange of the lanthanide or an analyte-cleavable caging group, respectively. The real-time three-color detection of up to three analytes was demonstrated, thus setting the stage for the non-invasive investigation of interconnected biological processes. [ABSTRACT FROM AUTHOR]

Deubiquitinases (DUBs) counteract ubiquitination by removing or trimming ubiquitin chains to alter the signal. Their diverse role in biological processes and involvement in diseases have recently attracted great interest with regard to their mechanism and inhibition. It has been shown that some DUBs are regulated by reactive oxygen species (ROS) in which the catalytic Cys residue undergoes reversible oxidation, hence modulating DUBs activity under oxidative stress. Reported herein for the first time, the observation that small molecules, which are capable of generating ROS efficiently, inhibit DUBs by selective and nonreversible oxidation of the catalytic Cys residue. Interestingly, the small molecule beta-lapachone, which is currently in clinical trials for cancer, is among the potent inhibitors, thus suggesting possible new cellular targets for its therapeutic effects. Our study describes a novel mechanism of DUBs inhibition and opens new opportunities in exploiting them for cancer therapy. [ABSTRACT FROM AUTHOR]

Platinum complexes are the most widely used anticancer drugs; however, new generations of agents are needed. The organoiridium(III) complex [(η5-Cpxbiph)Ir(phpy)(Cl)] ( 1-Cl), which contains π-bonded biphenyltetramethylcyclopentadienyl (Cpxbiph) and C^N-chelated phenylpyridine (phpy) ligands, undergoes rapid hydrolysis of the chlorido ligand. In contrast, the pyridine complex [(η5-Cpxbiph)Ir(phpy)(py)]+ ( 1-py) aquates slowly, and is more potent (in nanomolar amounts) than both 1-Cl and cisplatin towards a wide range of cancer cells. The pyridine ligand protects 1-py from rapid reaction with intracellular glutathione. The high potency of 1-py correlates with its ability to increase substantially the level of reactive oxygen species (ROS) in cancer cells. The unprecedented ability of these iridium complexes to generate H2O2 by catalytic hydride transfer from the coenzyme NADH to oxygen is demonstrated. Such organoiridium complexes are promising as a new generation of anticancer drugs for effective oxidant therapy. [ABSTRACT FROM AUTHOR]

Durch Anregung mit nahinfrarotem Licht (980 nm) können PEGylierte W18O49 ‐ Nanodrähte die Bildung von Singulettsauerstoff und damit reaktiven Sauerstoffspezies (ROS) sensibilisieren. Der daraus resultierende PDT ‐ Effekt kann zur Zerstörung von Tumoren in Abwesenheit organischer Photosensibilisatoren führen. PEG=Polyethylenglycol, PDT=photodynamische Therapie, PTT=photothermale Therapie. [ABSTRACT FROM AUTHOR]

Kupferionen (rote Kugel im Bild) akkumulieren in Amyloid ‐ β ‐ Plaques und spielen dort eine Rolle bei der Erzeugung reaktiver Sauerstoffspezies (ROS). Massenspektrometrische Studien zeigen, an welchen Stellen eine oxidative Schädigung auftritt, was neue Einblicke in den Mechanismus der ROS ‐ Produktion bietet und dadurch zum besseren Verständnis der Pathogenität von Amyloid ‐ β ‐ Peptiden beiträgt. [ABSTRACT FROM AUTHOR]

The article presents a study on a reactive oxygen species (ROS)-responsive polymer in gene delivery in cancer cells. It states that the ROS-responsive thioketal-based poly(amino thioketal) (PATK) was synthesized for safe, efficient, and targeted gene delivery in prostate cancer cells. Result shows that the DNA/PATK polyphlexes exhibited efficient gene transfection. Moreover, the high levels of intracellular ROS in cancer cells are biological stimuli that can be used for targeted gene delivery.

Die ROS waren′s nicht: Zwei aktuelle Arbeiten belegen, dass reaktive Sauerstoffspezies (ROS) nicht für den Zelltod von Bakterien nach Antibiotikabehandlung verantwortlich sind. Das Konzept der ROS kann damit nicht verallgemeinert auf alle Prozesse, die für den Zelltod verantwortlich sind, angewendet werden. Im Bereich der bakteriziden Antibiotika beginnt damit die Suche nach dem Mechanismus ihrer biologischen Wirkung erneut. [ABSTRACT FROM AUTHOR]

Ceroxid‐Zirconiumoxid‐Nanopartikel von 2 nm Größe und mit erhöhtem Ce3+‐Gehalt zeigen eine stark erhöhte Fähigkeit zum Abfangen reaktiver Sauerstoffspezies (ROS). S.‐H. Lee, T. Hyeon et al. beschreiben in der Zuschrift auf S. 11557 die überlegenen Eigenschaften von Ce0.7Zr0.3O2‐Nanopartikeln bei der Regulation von Entzündungszellen. Sie wirken als effiziente ROS‐Fänger gegen Multiorganversagen bei Sepsis und verringern so Mortalität und Entzündungsreaktionen. [ABSTRACT FROM AUTHOR]

W18O49 ‐ Nanodrähte können die Bildung von Singulettsauerstoff durch Bestrahlung mit NIR ‐ Licht sensibilisieren. In der Zuschrift auf S. 12558 ff. beschreiben K. C. Hwang et al. die komplette Zerstörung solider Tumoren in Mäusen mithilfe einer durch W18O49 ‐ Nanodrähte vermittelten photodynamischen Therapie (PDT). Dieser Effekt kann durch den Einsatz der photothermischen Therapie oder des Krebswirkstoffs Doxorubicin nicht erreicht werden. [ABSTRACT FROM AUTHOR]