Peroxidase activity of a Cu-Fe bimetallic hydrogel and applications for colorimetric detection of ascorbic acid.

A Cu-Fe bimetallic hydrogel (2-QF-CuFe-G) was constructed through a simple method. The 2-QF-CuFe-G metallohydrogel possesses excellent peroxidase-like activity to catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2. The catalytic mechanism was confirmed by the addition of •OH radical scavenger isopropyl alcohol (IPA), tert-butyl alcohol (TBA) and ˙OH trapping agent terephthalic acid (TA). Remarkably, the resultant blue ox-TMB system can be used to selectively and sensitively detect ascorbic acid (AA) with an LOD of 0.93 µM in the range of 4-36 µM through the colorimetric method. Moreover, the assay based on the 2-QF-CuFe-G metallohydrogel can be successfully applied to detect AA in fresh fruits.

White-light-emitting Ln-hydrogels with multi-stimuli responsiveness and applications in environmental sensing and anti-counterfeiting.

The construction of smart materials, especially white light emitting (WLE) hydrogels with multi-stimuli responsive properties, has received widespread attention from researchers. In this study, a WLE hydrogel was obtained by the in situ doping of Eu3+ and Tb3+ into a blue emission low molecular weight gelator (MPF). Remarkably, the prepared WLE hydrogel possessed excellent stimuli responsiveness to pH, temperature and chemicals, and could be used as a soft thermometer and a selective sensor for Cu2+. The correlated color temperature of the WLE hydrogel was calculated to be 5063 K, suggesting a potential application in cool white light. Moreover, a series of metallohydrogels with different colors were obtained by modulating the ratio of MPF, Eu3+ and Tb3+ or changing the excitation wavelength, which was an excellent candidate to construct soft materials of a full-color system. Additionally, the WLE hydrogel could be used for constructing anti-counterfeiting materials. Therefore, this study provides a new approach for preparing smart WLE hydrogels with multiple functions.

Piezoelectric Nanozyme for Dual-Driven Catalytic Eradication of Bacterial Biofilms.

Catalytic nanomedicine can in situ catalytically generate bactericidal species under external stimuli to defend against bacterial infections. However, bacterial biofilms seriously impede the catalytic efficacy of traditional nanocatalysts. In this work, MoSe2 nanoflowers (NFs) as piezoelectric nanozymes were constructed for dual-driven catalytic eradication of multi-drug-resistant bacterial biofilms. In the biofilm microenvironment, the piezoelectricity of MoSe2 NFs was cascaded with their enzyme-mimic activity, including glutathione oxidase-mimic and peroxidase-mimic activity. As a result, the oxidative stress in the biofilms was sharply elevated under ultrasound irradiation, achieving a 4.0 log10 reduction of bacterial cells. The in vivo studies reveal that the MoSe2 NFs efficiently relieve the methicillin-resistant Staphylococcus aureus bacterial burden in mice under the control of ultrasound at a low power density. Moreover, because of the surface coating of antioxidant poly(ethyleneimine), the dual-driven catalysis of MoSe2 NFs was retarded in normal tissues to minimize the off-target damage and favor the wound healing process. Therefore, the cascade of piezoelectricity and enzyme-mimic activity in MoSe2 NFs reveals a dual-driven strategy for improving the performance of catalytic nanomaterials in the eradication of bacterial biofilms.

A fluorescent probe based on a phenylalanine derivative is capable of sequential detection of Zn2+ and Cys/His.

A facile and dual fluorescent chemosensor (named 7-IDF) based on a phenylalanine derivative with an indole group was designed and synthesized. 7-IDF can selectively and sensitively detect Zn2+ via obvious fluorescence enhancement in an aqueous solution. Remarkably, the 7-IDF-Zn complex with blue luminescence has higher selectivity toward cysteine (Cys) and histidine (His) than for other amino acids. Intriguingly, 7-IDF can also be used as an excellent probe to detect Zn2+ in real water samples. Moreover, 7-IDF and 7-IDF-Zn possess excellent biocompatibility and cell permeability, and 7-IDF can consecutively detect Zn2+ and Cys/His in Hela cells through fluorescence imaging experiments. This study suggests that the phenylalanine-based chemosensor possesses great potential applications for the sequential detection of Zn2+ and Cys/His in biosystems.

Cold-catalytic antitumor immunity with pyroelectric black phosphorus nanosheets.

Catalytic nanomedicine with the innate features of catalysts brings incomparable properties to biomedicine over traditional drugs. The temperature-dependent activity of catalysts provides catalytic nanomedicines with a facile strategy to control their therapeutic performance. Tuning catalytic nanomedicine by cold treatment (4-37 °C) is safe and desired for practical applications, but there is a lack of cold-catalytic platforms. Herein, with black phosphorus (BP) as a model pyroelectric nanocatalyst, we explored the potential of cold-catalysts for antitumor therapy. BP nanosheets with pyro-catalytic activity catalyze the generation of oxidative stress to activate antitumor immunity under cold treatment. Due to the cold-catalytic immunomodulation, immune memory was successfully achieved to prevent tumor metastasis and recurrence. Considering the safety and conductive depth (>10 mm) of cold in the body, pyroelectric nanocatalysts open up exciting opportunities for the development of cold-catalytic nanomedicine.

Biocomputation with MnTiO3 Piezoelectric Enzymes for Programed Catalysis of Tumor Death.

Catalytic nanomedicine, especially artificial enzymes, exhibit obvious merits over traditional nanomedicine. However, the lack of controllability over an enzymatic process seriously challenges the therapeutic performance. Herein, we present a concept of using piezoelectric enzymes in combination with biocomputation ability. As a paradigm, MnTiO3 nanodisks were prepared with multiple enzyme-mimicking activity, including glutathione oxidase, peroxidase, and catalase. Different from the conventional artificial enzymes, the enzymatic activity of MnTiO3 nanodisks was activated by ultrasound and switched by a tumor microenvironment, which allows precise control over enzymatic catalysis in tumors. By virtue of the multiple artificial enzyme activity of MnTiO3 nanodisks, a biocomputing platform was constructed based on a Boolean logic-based algorithm. With ultrasound and tumor microenvironment as input signals, cytotoxicity was output via logic-based biocomputation for programed tumor killing. The concept of piezoelectric enzymes together with a biocomputation strategy provides an intelligent and effective approach for catalytic tumor eradication.

Amino acid derivative-based Ln-metallohydrogels with multi-stimuli responsiveness and applications.

Metallohydrogels and lanthanide (Ln) fluorescent materials have gained much attention recently. In this study, we designed and synthesized a facile gelator of a phenylalanine-based derivative containing an indazole group (namely IZF). It was found that IZF can self-assemble to form hydrogel at pH ≤ 7. Meanwhile, IZF and Tb3+/Eu3+ can co-assemble to generate IZF-Tb and IZF-Eu metallohydrogels with green and red fluorescence, respectively, at pH 8-11, with excellent multi-stimuli responsiveness. The bimetallic hydrogels of IZF-Tb/Eu exhibit different colors under UV light by adjusting the ratio of Tb3+ and Eu3+. Moreover, white light emission was achieved with IZF-Tb/Eu bimetallic gels through doping carbon dots (CDs) by tailoring the stoichiometric ratio of Ln-complex and CDs. Remarkably, IZF-Tb and IZF-Eu could be used as fluorescent inks with excellent stability. This study indicates that the amino acid derivative-based Ln-metallohydrogels are excellent candidates for constructing information storage and multiple anti-counterfeiting materials.

A Cascade Nanozyme with Amplified Sonodynamic Therapeutic Effects through Comodulation of Hypoxia and Immunosuppression against Cancer.

The tumor microenvironment (TME) featured by immunosuppression and hypoxia is pivotal to cancer deterioration and metastasis. Thus, regulating the TME to improve cancer cell ablation efficiency has received extensive interest in oncotherapy. However, to reverse the immunosuppression and alleviate hypoxia simultaneously in the TME are major challenges for effective cancer therapy. Herein, a multifunctional platform based on Au nanoparticles and a carbon dots modified hollow black TiO2 nanosphere (HABT-C) with intrinsic cascade enzyme mimetic activities is prepared for reversing immunosuppression and alleviating hypoxia in the TME. The HABT-C NPs possess triple-enzyme mimetic activity to act as self-cascade nanozymes, which produce sufficient oxygen to alleviate hypoxia and generate abundant ROS. The theoretical analysis demonstrates that black TiO2 facilitates absorption of H2O and O2, separation of electron-holes, and generation of ROS, consequently amplifying the sonodynamic therapy (SDT) efficiency. Specifically, HABT-C exhibits favorable inhibition of immunosuppressive mediator expression, along with infiltrating of immune effector cells into the TME and reversing the immunosuppression in the TME. As a result, HABT-C can effectively kill tumor cells via eliciting immune infiltration, alleviating hypoxia, and improving SDT efficiency. This cascade nanozyme-based platform (HABT-C@HA) will provide a strategy for highly efficient SDT against cancer by modulation of hypoxia and immunosuppression in the TME.

Revealing the catalytic pathway of a quinone-mediated oxygen reduction reaction in aprotic Li-O2 batteries.

Soluble redox species that facilitate the oxygen reduction reaction by mediating the LiO2 intermediate and consequently the formation of the Li2O2 have attracted considerable interest for Li-O2 batteries. Based on extensive radical studies, this work discloses a distinct solution reaction route when a quinone derivative was employed as a redox mediator.

A facile gelator based on phenylalanine derivative is capable of forming fluorescent Zn-metallohydrogel, detecting Zn2+ in aqueous solutions and imaging Zn2+ in living cells.

Supramolecular hydrogels are attracting soft materials with potential applications. In this study, we synthesized a facile gelator (named 2-QF) based on phenylalanine derivative with a Quinoline group. 2-QF can assemble to form hydrogels at room temperature in different colors under low pH values. Moreover, 2-QF was triggered to form a yellow metallohydrogel (2-QF-Zn) at high pH by the coordination between 2-QF and Zn2+. 2-QF-Zn metallohydrogel showed excellent multi-stimuli responsiveness, especially the reversible "on-off" luminescence switching, as induced by base/acid. In addition, at a low concentration, 2-QF can selectively and visibly identify Zn2+ through fluorescence enhancement, and can detect Zn2+ at physiological pH as a chemosensor. Remarkably, 2-QF and 2-QF-Zn exhibited an excellent biocompatibility without cell cytotoxicity, and 2-QF is able to penetrate live HeLa cells and image intracellular Zn2+ by a turn-on fluorescent response, which makes it a potential candidate for biomedical applications.

N-Confused Hexapyrrolic Phlorinoid with NIR Absorption: Synthesis, Fusion, Oxidation, and Copper(II) Coordination.

An N-confused hexapyrrolic phlorinoid 1 and its isomer N-fused hexapyrrolic phlorinoid 2 were synthesized through [4 + 2] condensation. Both 1 and 2 can be readily transformed into N-confused hexapyrrolic phlorinone 3 under aerobic conditions. Coordination of 1 with Cu(acac)2 afforded two different mono-Cu(II) complexes 4 and 5 with CNNN and ONNN coordination environments, respectively. The NIR absorption bands can be effectively modulated up to 1265 nm through the oxidation, fusion, and metalation reactions.

Integrated cascade nanozyme catalyzes in vivo ROS scavenging for anti-inflammatory therapy.

Here, an integrated cascade nanozyme with a formulation of Pt@PCN222-Mn is developed to eliminate excessive reactive oxygen species (ROS). This nanozyme mimics superoxide dismutase by incorporation of a Mn-[5,10,15,20-tetrakis(4-carboxyphenyl)porphyrinato]-based metal-organic framework compound capable of transforming oxygen radicals to hydrogen peroxide. The second mimicked functionality is that of catalase by incorporation of Pt nanoparticles, which catalyze hydrogen peroxide disproportionation to water and oxygen. Both in vitro and in vivo experimental measurements reveal the synergistic ROS-scavenging capacity of such an integrated cascade nanozyme. Two forms of inflammatory bowel disease (IBD; i.e., ulcerative colitis and Crohn's disease) can be effectively relieved by treatment with the cascade nanozyme. This study not only provides a new method for constructing enzyme-like cascade systems but also illustrates their efficient therapeutic promise in the treatment of in vivo IBDs.

Assembly of (l+d)-Tryptophan Derivatives Containing an Imidazole Group Selectively Forms a Rare Purple Ni2+-Hydrogel.

Design of metal-selective hydrogels is attractive due to potential applications in materials and biological sciences. Although much progress has been made, assembly of both l- and d-amino acid derivatives was less explored for design of metallohydrogels. In this study, we synthesized a facile and small tryptophan derivative containing an imidazole ligand with both l- and d- configurations (denoted as l/d-ImW). Intriguingly, the assembly of (l+d)-ImW gelators was found to selectively form a Ni2+-hydrogel in aqueous medium at room temperature, which shows a rare purple color and exhibits excellent multi-responsiveness. In addition to insights into the gelation mechanism, this study provides a novel approach to the design of metallohydrogels, by the assembly of (l+d)-amino acid derivatives containing both aromatic rings and multiple metal coordination sites.

Artificial Enzyme Catalyzed Cascade Reactions: Antitumor Immunotherapy Reinforced by NIR-II Light.

Current cancer therapy is seriously challenged by tumor metastasis and recurrence. One promising solution to these problems is to build antitumor immunity. However, immunotherapeutic efficacy is highly impeded by the immunosuppressive state of the tumors. Here a new strategy is presented, catalytic immunotherapy based on artificial enzymes. Cu2-x Te nanoparticles exhibit tunable enzyme-mimicking activity (including glutathione oxidase and peroxidase) under near-infrared-II (NIR-II) light. The cascade reactions catalyzed by the Cu2-x Te artificial enzyme gradually elevates intratumor oxidative stress to induce immunogenic cell death. Meanwhile, the continuously generated oxidative stress by the Cu2-x Te artificial enzyme reverses the immunosuppressive tumor microenvironment, and boosts antitumor immune responses to eradicate both primary and distant metastatic tumors. Moreover, immunological memory effect is successfully acquired after treatment with the Cu2-x Te artificial enzyme to suppress tumor relapse.

Unique Tyr-heme double cross-links in F43Y/T67R myoglobin: an artificial enzyme with a peroxidase activity comparable to that of native peroxidases.

The X-ray crystal structure of F43Y/T67R myoglobin revealed unique Tyr-heme double cross-links between Tyr43 and the heme 4-vinyl group, which represents a novel post-translational modification of heme proteins. Moreover, with the feature of a distal His-Arg pair, the designed artificial enzyme exhibited a peroxidase activity comparable to that of native peroxidases, such as the most efficient horseradish peroxidase.

Enhancement of protein stability by an additional disulfide bond designed in human neuroglobin.

Human neuroglobin (Ngb) forms an intramolecular disulfide bond between Cys46 and Cys55, with a third Cys120 near the protein surface, which is a promising protein model for heme protein design. In order to protect the free Cys120 and to enhance the protein stability, we herein developed a strategy by designing an additional disulfide bond between Cys120 and Cys15 via A15C mutation. The design was supported by molecular modeling, and the formation of Cys15-Cys120 disulfide bond was confirmed experimentally by ESI-MS analysis. Molecular modeling, UV-Vis and CD spectroscopy showed that the additional disulfide bond caused minimal structural alterations of Ngb. Meanwhile, the disulfide bond of Cys15-Cys120 was found to enhance both Gdn·HCl-induced unfolding stability (increased by ∼0.64 M) and pH-induced unfolding stability (decreased by ∼0.69 pH unit), as compared to those of WT Ngb with a single native disulfide bond of Cys46-Cys55. Moreover, the half denaturation temperature (T m) of A15C Ngb was determined to be higher than 100 °C. In addition, the disulfide bond of Cys15-Cys120 has slight effects on protein function, such as an increase in the rate of O2 release by ∼1.4-fold. This study not only suggests a crucial role of the artificial disulfide in protein stabilization, but also lays the groundwork for further investigation of the structure and function of Ngb, as well as for the design of other functional heme proteins, based on the scaffold of A15C Ngb with an enhanced stability.

Near-infrared light-responsive hydrogels via peroxide-decorated MXene-initiated polymerization.

Two-dimensional MXene Ti3C2T x nanosheets with peroxide decoration (p-Ti3C2T x ) are synthesized by a sonication-assisted MILD etching method. The obtained MXenes can generate hydroxyl radical species and act as an initiator for free-radical polymerization of a series of acrylic monomers without the use of light illumination or co-initiators. The monomers analyzed include acrylamide, N-isopropylacrylamide (NIPAM), N,N-dimethylacrylamide, methyl methacrylate, and hydroxyethyl methacrylate. By simply mixing N-isopropylacrylamide monomers and p-Ti3C2T x nanosheets under deoxygenated conditions, PNIPAM-based nanocomposite hydrogels are synthesized using a high concentration of the monomer. The nanocomposite hydrogels have a photothermal conversion efficiency of 34.7% and photothermal stability superior to that of pristine Ti3C2T x . Taking advantage of the thermal responsive behavior of PNIPAM, the nanocomposite hydrogels are successfully exploited as remotely near-infrared light controlled "smart" windows, fluidic valves and photodetectors.

A La3+-selective metallohydrogel with a facile gelator of a phenylalanine derivative containing an imidazole group.

The first La3+-selective metallohydrogel was constructed by using a facile gelator of a phenylalanine derivative containing an imidazole group, N-(1H-imidazol-4-yl)methylidene-l-phenylalanine, namely La-ImF, which exhibits multi-stimuli responsive properties, including to heat, shearing, pH, etc. Various measurements were also carried out to obtain insights into the mechanism of gelation. Moreover, the La-ImF hydrogel can adsorb toxic dyes, making it a potential candidate for sewage treatment.

A Chiral Ligand Assembly That Confers One-Electron O2 Reduction Activity for a Cu2+ -Selective Metallohydrogel.

The design of functional metallohydrogels is attractive but challenging. A rational approach is introduced for designing functional metallohydrogels using chiral ligands, a phenylalanine derivative with a pyridyl group (l/d-PF). Intriguingly, the as-prepared metallohydrogel exhibits excellent O2 binding and activating properties. Insights into the O2 binding pathway reveals the presence of a novel [(l+d)-PF-Cu3+ -O2- ] species, which can efficiently reduce ferric cytochrome c with the reactive O2- by receiving an electron from reductant ascorbic acid. This study provides helpful instructions for developing new artificial systems with specific functions through the effective combination of chiral ligands with metal ions.

Green and efficient biosynthesis of indigo from indole by engineered myoglobins.

With the demand nowadays for blue dyes, it is of practical importance to develop a green and efficient biocatalyst for the production of indigo. The design of artificial enzymes has been shown to be attractive in recent years. In a previous study, we engineered a single mutant of sperm whale myoglobin, F43Y Mb, with a novel Tyr-heme cross-link. In this study, we found that it can efficiently catalyze the oxidation of indole to indigo, with a yield as high as 54% compared to the highest yield (∼20%) reported to date in the literature. By further modifying the heme active site, we engineered a double mutant of F43Y/H64D Mb, which exhibited the highest catalytic efficiency (198 M-1 s-1) among the artificial enzymes designed in Mb. Moreover, both F43Y Mb and F43Y/H64D Mb were found to produce the indigo product with a chemoselectivity as high as ∼80%. Based on the reaction system, we also established a convenient and green dyeing method by dyeing a cotton textile during the biosynthesis of indigo, followed by further spraying the concentrated indigo, without the need of strong acids/bases or any reducing agents. The successful application of dyeing a white cotton textile with a blue color further indicates that the designed enzyme and the dyeing method have practical applications in the future.