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Iron species can participate in the Fenton or Fenton‐like reaction to generate oxidizing species that can cause oxidative damages to biomolecules and induce oxidative stress in the body. Furthermore, iron accumulation and oxidative stress have been shown to associate with the pathological progression of neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). In this review, the role of iron species in generating the most deleterious free radical species (ie, hydroxyl radical) and effects of this species in causing oxidative stress in vivo are described. The implications of oxidative stress and the recently recognized cell death pathway (ie, ferroptosis) to AD are addressed. Strategies to combat this neurodegenerative disease, such as iron chelation and antioxidant therapies, and future research directions on this aspect are also discussed.

Chemodynamic therapy (CDT) has emerged to be a frontrunner amongst reactive oxygen species‐based cancer treatment modalities. CDT utilizes endogenous H2O2 in tumor microenvironment (TME) to produce cytotoxic hydroxyl radicals (•OH) via Fenton or Fenton‐like reactions. While possessing advantages such as tumor specificity, no need of external stimuli, and low side effects, practical applications of CDT are still impeded owing to the heterogeneity, complexity, and reductive environment of TME. Over the past couple of years, strategies to enhance CDT for efficient tumor regression are in rapid development in synergy with the growth of nanomedicine. In this review, we initially outline the fundamental understanding of Fenton and Fenton‐like reactions and their relationship with CDT. Subsequently, the development in the design of nanosystems for CDT is highlighted in a general manner. Furthermore, recent advancement of the strategies to augment Fenton reactions in TME for enhanced CDT is discussed in detail. Finally, perspectives toward the future development of CDT for better therapeutic outcome are presented. This review is expected to draw attention for collaborative research on CDT in the best interest of its future clinical applications. Chemodynamic therapy (CDT) utilizes endogenous H2O2 in tumor microenvironment to produce cytotoxic hydroxyl radicals through Fenton or Fenton‐like reactions. This review outlines the fundamental understanding of Fenton and Fenton‐like reactions and their relationship with CDT and highlights recent research advancements in the design of nanosystems to augment Fenton or Fenton‐like reactions for enhanced CDT. Perspectives toward the future development of CDT strategies for higher therapeutic outcome are also discussed.

Benqiang Rao, Email raobenqiang@bjsjth.cn Xin Wang, Email winsun2011@163.comAbstract: The rapid advancements in nanotechnology have provided unprecedented opportunities for the clinical translation of vitamin C (VC) in cancer therapy. Although pharmacological doses of VC exhibit potent anti-tumor activities via multiple mechanisms—including selective pro-oxidative stress induction, metabolic inhibition, epigenetic modulation, and immune function enhancement—the clinical application of VC remains significantly hindered by its inherent instability, short biological half-life, and lack of tumor-specific targeting. Recent progress in the design and synthesis of VC and its derivatives combined with advanced nanocarriers has enabled precise delivery and efficient release of VC at tumor sites. In this review, we systematically summarize recent advances in nano-formulation strategies of VC, with a detailed discussion of lipid-based nanocarriers including liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), polymeric nanoparticles, as well as metal-based nanozyme delivery systems primarily composed of iron, copper, and manganese. These nano-systems not only significantly enhance the stability and circulation half-life of VC but also exploit tumor microenvironment-specific stimuli, such as pH, hydrogen peroxide (H2O2), and glutathione (GSH), to achieve responsive and precise drug release in cancer tissues. Notably, metal-based nanomaterials in combination with VC synergistically catalyze the Fenton reaction, markedly boosting reactive oxygen species (ROS) generation and demonstrating remarkable anti-tumor efficacy. Moreover, nanotechnology platforms have facilitated effective combination therapies involving VC with chemotherapeutic agents, photothermal catalysts, and immune agonists. Finally, this article highlights key challenges in the clinical translation of nano-formulated VC, including safety evaluation, scale-up production, and prediction of therapeutic efficacy. Future research directions in nano-drug design and exploration of synergistic mechanisms are proposed, providing theoretical guidance and practical insights for precise cancer therapy using VC-based nanomedicine.

The lack of effective lignin valorization technology remains a major barrier to utilize lignocellulose for producing biofuels and biochemicals. In this work, a new technology via the three‐phase three‐dimensional electro‐Fenton reaction was employed for the first time to convert lignin or its derived aromatics. The operating parameters were optimized by central composite design, which was controlled to prompt the synthesis of long‐chain fatty acids from lignin instead of degrading lignin to CO2. Under the optimized condition, the yields of palmitic acid and octadecanoic acid from lignin reached 138.41 and 112.31 mg/g, respectively. Key intermediators were identified during the electrolysis of lignin model compound using gas chromatography–quantitative time of flight mass spectrometry. The mechanism for the production of long‐chain fatty acids from lignin was proposed. Lignin successively underwent degradation, opening ring, and couple reactions and produced free radicals. This study is the first to report the conversion of lignin into the precursor of biodiesel or advanced biofuels through electro‐Fenton electrolysis at room temperature and atmosphere pressure. This study provides an environment‐friendly route for direct conversion of lignin into high‐value added products as a new strategy to valorize this undervalued component in lignocellulosic biomass. A new technology via the three‐phase three‐dimensional electro‐Fenton reaction was employed for the first time to convert lignin or its derived aromatics. The yields of palmitic acid and octadecanoic acid from lignin reached 138.41 and 112.31 mg/g, respectively. Lignin successively underwent degradation, opening ring, and couple reactions and produced free radicals. This study is the first to report the conversion of lignin into the precursor of biodiesel or advanced biofuels at room temperature and atmosphere pressure. This study provides an environment‐friendly route for direct conversion of lignin into high‐value added products to valorize this undervalued component in lignocellulosic biomass.

The impact of the site of the Fenton reaction, i.e., hydroxyl radical (•OH) generation, on cytotoxicity was investigated by estimating cell lethality in rat thymocytes. Cells were incubated with ferrous sulfate (FeSO4) and hydrogen peroxide (H2O2), or pre-incubated with FeSO4 and then H2O2 was added after medium was replaced to remove iron ions or after the medium was not replaced. Cell lethality in rat thymocytes was estimated by measuring cell sizes using flow cytometry. High extracellular concentrations of FeSO4 exerted protective effects against H2O2-induced cell death instead of enhancing cell lethality. The pre-incubation of cells with FeSO4 enhanced cell lethality induced by H2O2, whereas a pre-incubation with a high concentration of FeSO4 exerted protective effects. FeSO4 distributed extracellularly or on the surface of cells neutralized H2O2 outside cells. Cytotoxicity was only enhanced when the Fenton reaction, i.e., the generation of •OH, occurred inside cells. An assessment of plasmid DNA breakage showed that •OH induced by the Fenton reaction system did not break DNA. Therefore, the main target of intracellularly generated •OH does not appear to be DNA.

Textile wastewater often contains complex, carcinogenic dyes such as Direct Red-81, which pose serious environmental hazards due to their resistance to degradation. This study addresses the challenge of effectively removing such pollutants by comparing two treatment methods: adsorption using chemically activated coal fly ash (CFA) and advanced oxidation processes (AOPs) using the Fenton-like reaction with Mn 2 ⁺/H₂O₂. CFA was activated using KOH and H₂SO₄ solutions, and both methods were applied to treat textile wastewater containing Direct Red-81 dye. The results showed that the AOPs method with Mn 2 ⁺/H₂O₂ (0.5 g:200 mL) achieved superior removal efficiencies for the dye, biochemical oxygen demand (BOD), and chemical oxygen demand (COD), with removal rates reaching approximately 90%. Conversely, the adsorption process using CFA was more effective in removing total suspended solids (TSS), achieving over 90% removal. These findings suggest that while AOPs with Mn 2 ⁺/H₂O₂ are highly effective for degrading organic pollutants like dyes and reducing BOD and COD, CFA-based adsorption is more suitable for TSS removal. A combined treatment approach may therefore be recommended for comprehensive textile wastewater remediation.

A sample of mesoporous TiO2 (MT, specific surface area = 150 m2·g−1) and two samples of MT containing 2.5 wt.% Fe were prepared by either direct synthesis doping (Fe2.5-MTd) or impregnation (Fe2.5-MTi). Commercial TiO2 (Degussa P25, specific surface area = 56 m2 g−1) was used both as a benchmark and as a support for impregnation with either 0.8 or 2.5 wt.% Fe (Fe0.80-IT and Fe2.5-IT). The powders were characterized by X-ray diffraction, N2 isotherms at −196 °C, Energy Dispersive X-ray (EDX) Spectroscopy, X-ray Photoelectron Spectroscopy (XPS), Diffuse Reflectance (DR) ultra-violet (UV)-Vis and Mössbauer spectroscopies. Degradation of Acid Orange 7 (AO7) by H2O2 was the test reaction: effects of dark-conditions versus both UV and simulated solar light irradiation were considered. In dark conditions, AO7 conversion was higher with MT than with Degussa P25, whereas Fe-containing samples were active in a (slow) Fenton-like reaction. Under UV light, MT was as active as Degussa P25, and Fe doping enhanced the photocatalytic activity of Fe2.5-MTd; Fe-impregnated samples were also active, likely due to the occurrence of a photo-Fenton process. Interestingly, the Fe2.5-MTd sample showed the best performance under solar light, confirming the positive effect of Fe doping by direct synthesis with respect to impregnation.

The review considers the problem of hydrogen peroxide decomposition and hydroxyl radical formation in the presence of iron in vivo and in vitro. Analysis of the literature data allows us to conclude that, under physiological conditions, transport of iron, carried out with the help of carrier proteins, minimizes the possibility of appearance of free iron ions in cytoplasm of the cell. Under pathological conditions, when the process of transferring an iron ion from a donor protein to an acceptor protein can be disrupted due to modifications of the carrier proteins, iron ions can enter cytosol. However, at pH values close to neutral, which is typical for cytosol, iron ions are converted into water-insoluble hydroxides. This makes it impossible to decompose hydrogen peroxide according to the mechanism of the classical Fenton reaction. A similar situation is observed in vitro, since buffers with pH close to neutral are used to simulate free radical oxidation. At the same time, iron hydroxides are able to catalyze decomposition of hydrogen peroxide with formation of a hydroxyl radical. Decomposition of hydrogen peroxide with iron hydroxides is called Fenton-like reaction. Studying the features of Fenton-like reaction in biological systems is the subject of future research.

The noninvasive nature of photodynamic therapy (PDT) enables the preservation of organ function in cancer patients. However, PDT is impeded by hypoxia in the tumor microenvironment (TME) caused by high intracellular oxygen (O ) consumption and distorted tumor blood vessels. Therefore, increasing oxygen generation in the TME would be a promising methodology for enhancing PDT. Herein, we proposed a concept of ferroptosis-promoted PDT based on the biochemical characteristics of cellular ferroptosis, which improved the PDT efficacy significantly by producing reactive oxygen species (ROS) and supplying O sustainably through the Fenton reaction. In contrast to traditional strategies that increase O based on decomposition of limited concentration of hydrogen peroxide (H O ), our methodology could maintain the concentration of H O and O through the Fenton reaction. : For its association with sensitivity to ferroptosis, solute carrier family 7 member 11 (SLC7A11) expression was characterized by bioinformatics analysis and immunohistochemistry of oral tongue squamous cell carcinoma (OTSCC) specimens. Afterwards, the photosensitizer chlorin e6 (Ce6) and the ferroptosis inducer erastin were self-assembled into a novel supramolecular Ce6-erastin nanodrug through hydrogen bonding and π-π stacking. Then, the obtained Ce6-erastin was extensively characterized and its anti-tumor efficacy towards OTSCC was evaluated both and . : SLC7A11 expression is found to be upregulated in OTSCC, which is a potential target for ferroptosis-mediated OTSCC treatment. Ce6-erastin nanoparticles exhibited low cytotoxicity to normal tissues. More significantly, The over-accumulated intracellular ROS, increased O concentration and inhibited SLC7A11 expression lead to enhanced toxicity to CAL-27 cells and satisfactory antitumor effects to xenograft tumour mouse model upon irradiation. : Our ferroptosis promoted PDT approach markedly enhances anticancer actions by relieving hypoxia and promoting ROS production, thereby our work provides a new approach for overcoming hypoxia-associated resistance of PDT in cancer treatment.

Although heterogeneous photo‐Fenton reactions on nanoparticulate iron oxides effectively degrade organic pollutants, the underlying surface mechanisms remain debated. Here, we demonstrate how these pathways are modulated by specific hematite crystal facets. To investigate the influence of particle surface structure, methylene blue (MB) adsorption and photodegradation kinetics are examined using facet‐engineered hematite nanoparticles with distinct exposed facets. The results reveal that MB photodegradation strongly depends on both pH and facet orientation. When normalized by surface area, (116) facet shows higher photodegradation activity than those with (104) or (001) facets. This enhanced activity is attributed to favorable electronic structure and surface characteristics, including a smaller optical bandgap, faster charge transfer, and superior H2O2 decomposition. In contrast, the photodegradation capacity follows (104) 〉 (116) 〉 (001), primarily due to the higher density of surface‐active sites on the (104) facet. These sites promote coupled MB adsorption and degradation, enabling removal of a greater overall quantity of MB. Additionally, under high pH conditions, hematite can degrade MB in the dark, with capacities following (001) ≫ (116) 〉 (104). These findings underscore the critical catalytic role of specific hematite surfaces and advance the understanding of facet‐dependent photoinduced redox chemistry at mineral–water interfaces. This study reveals how hematite crystal facets govern heterogeneous (photo)‐Fenton degradation of organic dyes. Facet‐dependent differences in H2O2 decomposition and reactive oxygen species generation are demonstrated, providing mechanistic insights that inform environmental strategies for water purification and pollutant remediation.