Simultaneous Fenton‐like Ion Delivery and Glutathione Depletion by MnO2‐Based Nanoagent to Enhance Chemodynamic Therapy

Chemodynamic therapy (CDT) utilizes iron‐initiated Fenton chemistry to destroy tumor cells by converting endogenous H₂O₂ into the highly toxic hydroxyl radical (^.OH). There is a paucity of Fenton‐like metal‐based CDT agents. Intracellular glutathione (GSH) with ^.OH scavenging ability greatly reduces CDT efficacy. A self‐reinforcing CDT nanoagent based on MnO₂ is reported that has both Fenton‐like Mn²⁺ delivery and GSH depletion properties. In the presence of HCO₃^?, which is abundant in the physiological medium, Mn²⁺ exerts Fenton‐like activity to generate ^.OH from H₂O₂. Upon uptake of MnO₂‐coated mesoporous silica nanoparticles (MS@MnO₂ NPs) by cancer cells, the MnO₂ shell undergoes a redox reaction with GSH to form glutathione disulfide and Mn²⁺, resulting in GSH depletion‐enhanced CDT. This, together with the GSH‐activated MRI contrast effect and dissociation of MnO₂, allows MS@MnO₂ NPs to achieve MRI‐monitored chemo–chemodynamic combination therapy.     

Protein nanoparticles containing Cu(II) and DOX for efficient chemodynamic therapy via self-generation of H2O2

Chemodynamic therapy (CDT) refers to generating hydroxyl radical (OH) in tumor sites via hydrogen peroxide (H₂O₂) catalyzed by transition metal ions in cancer cells under acidic environment. However, H₂O₂ content is not enough for effective CDT, although H₂O₂ content in cancer cells is higher than that of normal cells. Herein, we synthesized DOX@BSA-Cu NPs (nanoparticles) for effective CDT by providing enhanced content of H₂O₂ in cancer cells. The results proved Cu²⁺ in NPs could be reduced to Cu⁺ by glutathione (GSH) and effectively converted H₂O₂ to OH. Moreover, the loaded low-dose doxorubicin (DOX) in the NPs could improve the content of H₂O₂ and resulted in more efficient generation of OH in cancer cells. Thus DOX@BSA-Cu NPs exhibited higher cytotoxicity to cancer cells. This research may provide new ideas for the further studies on more effective Cu(II)-based CDT nanoagents.     

Efficient Fe(III)/Fe(II) cycling triggered by MoO2 in Fenton reaction for the degradation of dye molecules and the reduction of Cr(VI)

There is a relatively low efficiency of Fe(III)/Fe(II) conversion cycle and H₂O₂ decomposition (<30%) in conventional Fenton process, which further results in a low production efficiency of OH and seriously restricts the application of Fenton. Herein, we report that the commercial MoO₂ can be used as the cocatalyst in Fenton process to dramatically accelerate the oxidation of Lissamine rhodamine B (L-RhB), where the efficiency of Fe(III)/Fe(II) cycling is greatly enhanced in the Fenton reaction meanwhile. And the L-RhB solution could be degraded nearly 100% in 1 min in the MoO₂ cocatalytic Fenton system under the optimal reaction condition, which is apparently better than that of the conventional Fenton system (～50%). Different from the conventional Fenton reaction where the OH plays an important role in the oxidation process, it shows that ¹O₂ contributes most in the MoO₂ cocatalytic Fenton reaction. However, it is found that the exposed Mo⁴⁺ active sites on the surface of MoO₂ powders can greatly promote the rate-limiting step of Fe³⁺/Fe²⁺ cycle conversion, thus minimizing the dosage of H₂O₂ (0.400 mmol/L) and Fe²⁺ (0.105 mmol/L). Interestingly, the MoO₂ cocatalytic Fenton system also exhibits a good ability for reducing Cr(VI) ions, where the reduction ability for Cr(VI) reaches almost 100% within 2 h. In short, this work shows a new discovery for MoO₂ cocatalytic advanced oxidation processes (AOPs), which devotes a lot to the practical water remediation application.     

Host-guest interactions based supramolecular complexes self-assemblies for amplified chemodynamic therapy with H2O2 elevation and GSH consumption properties

Although endogenous H₂O₂ is overexpressed in tumor tissue, the amount of endogenous H₂O₂ is still insufficient for chemodynamic therapy (CDT). In addition, the abundant cellular glutathione (GSH) could also consume ^?OH for reduced CDT. Thus, the elevation of H₂O₂ and the consumption of GSH in tumor tissue are essential for the increased ^?OH yield and amplified CDT efficacy. In this paper, host-guest interactions based supramolecular complexes self-assemblies (SCSAs) were fabricated by incorporating cinnamaldehyde (CA) and PEG-modified cyclodextrin host units (mPEG-CD-CA) with ferrocene-(phenylboronic acid pinacol ester) conjugates (Fc-BE) on the basis of CD-induced host-guest interactions. After being internalized by cancer cells, CA can be released from SCSAs through the pH-responsive acetal linkage, elevating the H₂O₂ level by activating NADPH oxidase. Then, Fc can catalyze the H₂O₂ to higher cytotoxic hydroxyl radicals (^?OH). Moreover, quinone methide (QM) can be produced through H₂O₂-induced aryl boronic ester rearrangement and further consume the antioxidant GSH. In vitro and in vivo experiments demonstrate that SCSAs can be provided as potential amplified CDT nanoagents.     

Enzyme-Triggered Chemodynamic Therapy via a Peptide-H2S Donor Conjugate with Complexed Fe2+

Inducing high levels of reactive oxygen species (ROS) inside tumor cells is a cancer therapy method termed chemodynamic therapy (CDT). Relying on delivery of Fenton reaction promoters such as Fe²⁺, CDT takes advantage of overproduced ROS in the tumor microenvironment. We developed a peptide-H₂S donor conjugate, complexed with Fe²⁺, termed AAN - PTC – Fe²⁺ . The AAN tripeptide was specifically cleaved by legumain, an enzyme overexpressed in glioma cells, to release carbonyl sulfide (COS). Hydrolysis of COS by carbonic anhydrase formed H₂S, an inhibitor of catalase, an enzyme that detoxifies H₂O₂. Fe²⁺ and H₂S together increased intracellular ROS levels and decreased viability in C6 glioma cells compared with controls lacking either Fe²⁺, the AAN sequence, or the ability to generate H₂S. AAN - PTC – Fe²⁺ performed better than temezolimide while exhibiting no cytotoxicity toward H9C2 cardiomyocytes. This study provides an H₂S-amplified, enzyme-responsive platform for synergistic cancer treatment.     

In situ synthesis of red fluorescent gold nanoclusters with enzyme-like activity for oxidative stress amplification in chemodynamic therapy

Chemodynamic therapy（CDT） has attracted tremendous interest in cancer therapy because it is independent of oxygen and photoirradiation.However,the therapeutic efficacy of CDT is restricted by insufficient H₂ O₂ levels in tumor cells.Herein,employing endogenous GSH as a template and cationic polymeric chitosan（CS） as crosslinker and stabilizer exhibiting easy cell uptake,red luminescent gold nanoclusters（denoted CS-GSH@AuNCs） were successfully synthesized in HeLa cells.The i...     

Ultrafast O2 activation by copper oxide for 2,4-dichlorophenol degradation: The size-dependent surface reactivity

This study demonstrated interesting ultrafast activation of molecular O₂ by copper oxide (CuO) particles and very rapid elimination of aqueous 2,4-dichlorophenol (2,4-DCP) within reaction time of 30 s. Electron paramagnetic resonance (EPR) characterization indicated that OH, Cu³⁺, ¹O₂ and O₂⁻ were generated in the CuO/O₂ systems, wherein O₂⁻ would be the main reactive species responsible for 2,4-DCP degradation. It was further found that the catalytic ability of CuO for O₂ activation was highly size dependent and nano-CuO was far reactive than micro-CuO. H₂ temperature-programmed reduction (H₂-TPR), X-ray photoelectron spectroscopy (XPS) and vibrating sample magnetometer (VSM) analyses revealed that both the quantity and the reactivity of the surface reaction sites (surface Cu⁺ and O₂) could determine the catalytic ability of CuO affecting efficient Cu⁺-based molecular oxygen activation. Moreover, the O₂ activation ability of CuO would depend on not only the dimension, but also crystalline factors, for example, the exposed facets.     

Synthesis of Iron Nanometallic Glasses and Their Application in Cancer Therapy by a Localized Fenton Reaction

Metallic glasses and cancer theranostics are emerging fields that do not seem to be related to each other. Herein, we report the facile synthesis of amorphous iron nanoparticles (AFeNPs) and their superior physicochemical properties compared to their crystalline counterpart, iron nanocrystals (FeNCs). The AFeNPs can be used for cancer theranostics by inducing a Fenton reaction in the tumor by taking advantage of the mild acidity and the overproduced H₂O₂ in a tumor microenvironment: Ionization of the AFeNPs enables on‐demand ferrous ion release in the tumor, and subsequent H₂O₂ disproportionation leads to efficient ^.OH generation. The endogenous stimuli‐responsive ^.OH generation in the presence AFeNPs enables a highly specific cancer therapy without the need for external energy input.     

Tumor microenvironment-responsive MnSiO3-Pt@BSA-Ce6 nanoplatform for synergistic catalysis-enhanced sonodynamic and chemodynamic cancer therapy

Compared with traditional photodynamic therapy （PDT）,ultrasound （US） triggered sonodynamic therapy （SDT） has a wide application prospect in tumor therapy because of its deeper penetration depth.Herein,a novel MnSiO₃-Pt （MP） nanocomposite composed of Mn Si O₃nanosphere and noble metallic Pt was successfully constructed.After modification with bovine serum albumin （BSA） and chlorine e6 （Ce6）,the multifunctional nanoplatform Mn Si O₃-Pt@BSA-Ce6 （MPBC） realized the m...     

Fast and Long-Lasting Iron(III) Reduction by Boron Toward Green and Accelerated Fenton Chemistry

Generation of hydroxyl radicals in the Fenton system (Fe^II/H₂O₂) is seriously limited by the sluggish kinetics of Fe^III reduction and fast Fe^III precipitation. Here, boron crystals (C-Boron) remarkably accelerate the Fe^III/Fe^II circulation in Fenton-like systems (C-Boron/Fe^III/H₂O₂) to produce a myriad of hydroxyl radicals with excellent efficiencies in oxidative degradation of various pollutants. The surface B−B bonds and interfacial suboxide boron in the surface B₁₂ icosahedra are the active sites to donate electrons to promote fast Fe^III reduction to Fe^II and further enhance hydroxyl radical production via Fenton chemistry. The C-Boron/Fe^III/H₂O₂ system outperforms the benchmark Fenton (Fe^II/H₂O₂) and Fe^III-based sulfate radical systems. The reactivity and stability of crystalline boron is much higher than the popular molecular reducing agents, nanocarbons, and other metal/metal-free nanomaterials.     

Fast and Long‐Lasting Iron(III) Reduction by Boron Toward Green and Accelerated Fenton Chemistry

Generation of hydroxyl radicals in the Fenton system (Fe^II/H₂O₂) is seriously limited by the sluggish kinetics of Fe^III reduction and fast Fe^III precipitation. Here, boron crystals (C‐Boron) remarkably accelerate the Fe^III/Fe^II circulation in Fenton‐like systems (C‐Boron/Fe^III/H₂O₂) to produce a myriad of hydroxyl radicals with excellent efficiencies in oxidative degradation of various pollutants. The surface B?B bonds and interfacial suboxide boron in the surface B₁₂ icosahedra are the active sites to donate electrons to promote fast Fe^III reduction to Fe^II and further enhance hydroxyl radical production via Fenton chemistry. The C‐Boron/Fe^III/H₂O₂ system outperforms the benchmark Fenton (Fe^II/H₂O₂) and Fe^III‐based sulfate radical systems. The reactivity and stability of crystalline boron is much higher than the popular molecular reducing agents, nanocarbons, and other metal/metal‐free nanomaterials.     

Enhanced visible light photocatalytic activity of CeO2@Zn0.5Cd0.5S by facile Ce(IV)/Ce(III) cycle

In this study, CeO₂@Zn_0.5Cd_0.5S heterostructure (Ce@ZCS) is synthesized via a simple two-step hydrothermal method. The effect of CeO₂ loading on the visible-light photoactivity of Zn_0.5Cd_0.5S is mainly investigated. It is found that Ce@ZCS shows a 1.9 times activity as high as ZCS for the MB degradation. The improved activity mainly results from the significant enhanced charge separation by CeO₂, in which the electron transfer is obviously promoted by the facile Ce(IV)/Ce(III) cycle. The excited electrons of ZCS is easy to transfer to CeO₂, thus obviously increasing the charge separation of ZCS. The accepted electrons by CeO₂ may easily be captured by the adsorbed O₂ to form O₂⁻, and then O₂⁻ could combine with H⁺/H₂O to form HO₂, and OH. Finally, O₂⁻, h⁺ and OH are confirmed as the major oxidative species in photocatalytic reaction for Ce@ZCS, and a possible photocatalytic mechanism is proposed. The cheap, efficient Ce@ZCS photocatalyst could be applied for practical waste water treatment.     

Photo‐Fenton and Riboflavin‐photosensitized Processes of the Isoxaflutole Herbicide

The proherbicide Isoxaflutole (IXF) hydrolyzes spontaneously to diketonitrile (DKN) a phytotoxic compound with herbicidal activity. In this work, the sensitized degradation of IXF using Riboflavin (Rf), a typical environmentally friendly sensitizer, Fenton and photo‐Fenton processes has been studied. The results indicate that only the photo‐Fenton process produces a significant degradation of the IXF. Photolysis experiments of IXF sensitized by Riboflavin is not a meaningful process, IXF quenches the Rf excited triplet (³Rf*) state with a quenching rate constant of 1.5 · 10⁷ m ^?1 s^?1 and no reaction is observed with the species O₂(¹Δ_g) or ${\mathrm{O}}_2^{·?}$ generated from ³Rf*. The Fenton reaction produces no changes in the IXF concentration. While the photo‐Fenton process of the IXF, under typical conditions, it produces a degradation of 99% and a mineralization to CO₂ and H₂O of 88%. A rate constant value of 1.0 × 10⁹ m ^?1 s^?1 was determined for the reaction between IXF and HO˙. The photo‐Fenton process degradation products were identified by UHPLC‐MS/MS analysis.     

Synergistic cocatalytic effect of MoO3 and creatinine on Cu–Fenton reactions for efficient decomposition of H2O2

The key scientific problems with conventional Fenton reactions are the acidic pH dependence and low ROS production due to inefficient decomposition of H₂O₂. Although Cu–Fenton reactions can break the pH limitation, there is still an urgent need to improve the overall reaction efficiency, and thus broaden its applicability. Herein, we describe a synergistic strategy by introducing MoO₃ cocatalyst and creatinine (Cr) assistant to enhance the efficiency of Cu–Fenton reactions at near-neutral pH. In this strategy, Cu²⁺ interacts with Cr to form a complex (CuCr₂), which is then mainly linked to MoO₃ via the Cu²⁺ binding site (CuCr₂/MoO₃). Experimental and theoretical calculation results manifest that the CuCr₂/MoO₃ exhibits an excellent cocatalytic activity, which significantly facilitates the rate-limiting step of Cu–Fenton reactions, and enables the efficient decomposition of H₂O₂ for the generation of three reactive oxygen species (ROS, ?OH, ¹O₂, ?O₂^?). More significantly, this cocatalytic system with high oxidation activity can be applied for the detection of Cu²⁺ and ROS-based chemodynamic therapy (CDT), as well as sterilization of Escherichia coli. This study represents a new breakthrough in improving the efficiency of Fenton-based reactions with a facile and promising strategy, and drives great progress in practicality.     

Graphenes as Efficient Metal‐Free Fenton Catalysts

Reduced graphene oxide exhibits high activity as Fenton catalyst with HO^. radical generation efficiency over 82 % and turnover numbers of 4540 and 15023 for phenol degradation and H₂O₂ consumption, respectively. These values compare favorably with those achieved with transition metals, showing the potential of carbocatalysts for the Fenton reaction.     

Tumor Microenvironment Stimuli-Responsive Fluorescence Imaging and Synergistic Cancer Therapy by Carbon-Dot–Cu2+ Nanoassemblies

A method is developed to fabricate tumor microenvironment (TME) stimuli-responsive nanoplatform for fluorescence (FL) imaging and synergistic cancer therapy via assembling photosensitizer (chlorine e6, Ce6) modified carbon dots (CDs-Ce6) and Cu²⁺. The as-obtained nanoassemblies (named Cu/CC nanoparticles, NPs) exhibit quenched FL and photosensitization due to the aggregation of CDs-Ce6. Their FL imaging and photodynamic therapy (PDT) functions are recovered efficiently once they entering tumor sites by the stimulation of TME. Introducing of Cu²⁺ not only provides extra chemodynamic therapy (CDT) function through reaction with hydrogen peroxide (H₂O₂), but also depletes GSH in tumors by a redox reaction, thus amplifying the intracellular oxidative stress and enhancing the efficacy of reactive oxygen species (ROS) based therapy. Cu/CC NPs can act as a FL imaging guided trimodal synergistic cancer treatment agent by photothermal therapy (PTT), PDT, and thermally amplified CDT.     

Catalytic Hydroxylation of Benzene to Phenol by Dioxygen with an NADH Analogue

Hydroxylation of benzene by molecular oxygen (O₂) occurs efficiently with 10‐methyl‐9,10‐dihydroacridine (AcrH₂) as an NADH analogue in the presence of a catalytic amount of Fe(ClO₄)₃ or Fe(ClO₄)₂ with excess trifluoroacetic acid in a solvent mixture of benzene and acetonitrile (1:1 v/v) to produce phenol, 10‐methylacridinium ion and hydrogen peroxide (H₂O₂) at 298 K. The catalytic oxidation of benzene by O₂ with AcrH₂ in the presence of a catalytic amount of Fe(ClO₄)₃ is started by the formation of H₂O₂ from AcrH₂, O₂, and H⁺. Hydroperoxyl radical (HO₂^.) is produced from H₂O₂ with the redox pair of Fe³⁺/Fe²⁺ by a Fenton type reaction. The rate‐determining step in the initiation is the proton‐coupled electron transfer from Fe²⁺ to H₂O₂ to produce HO^. and H₂O. HO^. abstracts hydrogen rapidly from H₂O₂ to produce HO₂^. and H₂O. The Fe³⁺ produced was reduced back to Fe²⁺ by H₂O₂. HO₂^. reacts with benzene to produce the radical adduct, which abstracts hydrogen from AcrH₂ to give the corresponding hydroperoxide, accompanied by generation of acridinyl radical (AcrH^.) to constitute the radical chain reaction. Hydroperoxyl radical (HO₂^.), which was detected by using the spin trap method with EPR analysis, acts as a chain carrier for the two radical chain pathways: one is the benzene hydroxylation with O₂ and the second is oxidation of an NADH analogue with O₂ to produce H₂O₂.     

Facile Synthesis of Fe3O4@Au/PPy-DOX Nanoplatform with Enhanced Glutathione Depletion and Controllable Drug Delivery for Enhanced Cancer Therapeutic Efficacy

The complex physiological environment and inherent self-healing function of tumors make it difficult to eliminate malignant tumors by single therapy. In order to enhance the efficacy of antitumor therapy, it is significant and challenging to realize multi-mode combination therapy by utilizing/improving the adverse factors of the tumor microenvironment (TME). In this study, a novel Fe₃O₄@Au/PPy nanoplatform loaded with a chemotherapy drug (DOX) and responsive to TME, near-infrared (NIR) laser and magnetic field was designed for the combination enhancement of eliminating the tumor. The Fe²⁺ released at the low pH in TME can react with endogenous H₂O₂ to induce toxic hydroxyl radicals (·OH) for chemodynamic therapy (CDT). At the same time, the generated Fe³⁺ could deplete overexpressed glutathione (GSH) at the tumor site to prevent reactive oxygen species (ROS) from being restored while producing Fe²⁺ for CDT. The designed Fe₃O₄@Au/PPy nanoplatform had high photothermal (PT) conversion efficiency and photodynamic therapy (PDT) performance under NIR light excitation, which can promote CDT efficiency and produce more toxic ROS. To maximize the cancer-killing efficiency, the nanoplatform can be successfully loaded with the chemotherapeutic drug DOX, which can be efficiently released under NIR excitation and induction of slight acidity at the tumor site. In addition, the nanoplatform also possessed high saturation magnetization (20 emu/g), indicating a potential magnetic targeting function. In vivo and in vitro results identified that the Fe₃O₄@Au/PPy-DOX nanoplatform had good biocompatibility and magnetic-targeted synergetic CDT/PDT/PTT/chemotherapy antitumor effects, which were much better than those of the corresponding mono/bi/tri-therapies. This work provides a new approach for designing intelligent TME-mediated nanoplatforms for synergistically enhancing tumor therapy.     

Formation of the CuII–Phenoxyl Radical by Reaction of O2 with a CuII–Phenolate Complex via the CuI–Phenoxyl Radical

Reaction of Cu(ClO₄)₂ ⋅ 6 H₂O with a tripodal 2N2O ligand, H₂Me₂NL, having a p-(dimethylamino)phenol moiety, in CH₂Cl₂/MeOH (1:1 v/v) under basic conditions under an inert gas atmosphere gave [Cu(Me₂NL)(H₂O)] ( 1 ). The same reaction carried out under aerobic conditions gave [Cu(Me₂NL)(MeOH)]ClO₄ ( 2 ), which could be obtained also from the isolated complex 1 by reaction with O₂ in CH₂Cl₂/MeOH. The X-ray crystal structures of 1 and 2 revealed similar square-pyramidal structures, but 2 showed the (dimethylamino)phenoxyl radical features. Complex 1 exhibits characteristic Cu^II EPR signals of the d ground state in CH₂Cl₂/MeOH at 77 K, whereas 2 is EPR-silent. The EPR and X-ray absorption fine structure (XAFS) results suggest that 2 is assigned to the Cu^II–(dimethylamino)phenoxyl radical. However, complex 1 showed different features in the absence of MeOH. The EPR spectrum of the CH₂Cl₂ solution of 1 exhibits distortion from the d ground state and a temperature-dependent equilibrium between the Cu^II–(dimethylamino)phenolate and the Cu^I–(dimethylamino)phenoxyl radical. From these results, Cu^II–phenoxyl radical complex 2 is concluded to be formed by the reaction of 1 with O₂ via the Cu^I–phenoxyl radical species.     

Triple-Layered Metal-Organic Framework Hybrid for Tandem Response-Driven Enhanced Chemotherapy

The precise release of drugs is essential to improve cancer therapeutic efficacy. In this work, a tandem responsive strategy was developed based on a triple-layered metal-organic framework (MOF) hybrid. The MOF nanoprobe was stepwise fabricated with a telomerase-responsive inner, a pH-sensitive MOF filling and H₂O₂-responsive coordination complex shell of Fe³⁺ and eigallocatechin gallate (EGCG). In the tumor microenvironment, the shell was dissociated by endogenous H₂O₂ and simultaneously produced highly reactive hydroxyl radicals by a Fenton reaction. Meanwhile, the released EGCG could downregulate the expression of P-glycoprotein responsible for drug resistance. After the dissociation of the framework by protons, telomerase could trigger the release of the drug from the DNA duplex on the exposed inner shell. By integrating confined drug release, inhibited efflux pump and chemodynamic therapy, the all-in-one chemotherapy strategy was identified with enhanced therapeutic efficacy in drug-resistant cancer cells.