ROS Generation Research Articles

Metal-organic frameworks (MOFs) are an emerging class of porous materials with remarkable surface area, tunable pore structures, and diverse chemical functionalities. In this study, we reported the green synthesis and comprehensive characterization of a novel modified NH2-MIL-101 (Cu) derived from 2-aminoterephthalic acid, followed by post-synthetic modification with terephthalaldehyde to improve its adsorption capabilities. The synthesized Cu-MOF exhibited a very high specific surface area (2037.65m2·g-1, BET), a total pore volume of 0.7465cm2·g-1 and mesoporosity with an average pore diameter of 29.06nm. SEM and TEM images showed uniform polyhedral particles with an average particle size of ≈ 85 ± 10nm, while XRD patterns displayed well-defined diffraction peaks with the most intense reflection at ~ 2θ = 28-29°, confirming high crystallinity and preservation of the MIL-101 topology after modification. Under optimized conditions (10mg adsorbent, 10 mL solution, room temperature and appropriate pH), the material exhibited high adsorption capacities of 230.1, 165.2, and 187.4mg·g-1 for crystal violet, methyl orange, and rhodamine B, respectively, attributable to its large porosity and functional surface groups. A plausible mechanism involving electrostatic interaction, π-π stacking, and coordination bonding is proposed for adsorption of dyes onto the modified MOF. The Cu-MOF maintained excellent structural stability and reusability, retaining over 92% of its initial adsorption capacity after five consecutive adsorption-desorption cycles, as confirmed by XRD patterns showing no noticeable framework collapse. This highlights its robustness and potential for sustainable wastewater remediation. In addition to dye removal, the material demonstrated antimicrobial activity, with MIC values of 4, 8, 32 and 128µg/mL for P. aeruginosa, C. albicans, E. coli, and A. fumigatus, respectively, while no inhibition was observed against Gram-positive strains at concentrations up to 4096µg/mL. The antimicrobial effect is likely attributed to Cu2+ ion release and electrostatic interactions leading to membrane disruption and ROS generation. These results highlight the potential of the synthesized Cu-MOF as a multifunctional and eco-friendly candidate for both wastewater treatment and biomedical applications.

Ammonia-induced T lymphocyte death (AITD) offers a new perspective on immune regulation after the activation of CD8+ T cells. However, the use of a single AITD inhibitor is constrained by multiple factors in the immunosuppressive tumor microenvironment and requires combination strategies to achieve breakthroughs. Herein, a rationally designed organic nanozyme (IR-IHpd) is presented, integrating anthocyanin-based near-infrared photodynamic therapy (NIR-PDT) and Hemin-derived peroxidase (POD)-like catalytic activity. Under 780nm laser irradiation, it generates ROS through Type I/II photodynamic mechanisms while catalyzing H2O2 into cytotoxic ·OH, establishing an uninterrupted ROS generation. Co-encapsulated with CB-839 in DSPE-Hyd-PEG and coated with dendritic cell (DC) membranes to form a biomimetic system (DMIC), this system targets both tumors and T cells. After intravenous administration, the DMIC nanozyme system efficiently accumulates in tumor tissues, tumor-draining lymph nodes, and spleens, where NIR irradiation induces tumor immunogenic cell death while promoting DCs maturation and T cell activation. The DMIC also functions as a tumor vaccine, capable of directly activating T cells and preventing tumor occurrence. Furthermore, the released CB-839 reduces intracellular ammonia levels in T cells, thereby enhancing anti-tumor immunity. This pioneering work achieves targeted AITD inhibition for the first time, integrating NIR-PDT, metabolic modulation, and immune activation to advance nanozyme-based immunotherapy.

Coronary heart disease remains one of the leading causes of death worldwide. Myocardial ischaemia-reperfusion injury, the underlying cause of сoronary heart disease, involves the excessive formation of reactive oxygen species, which leads to myocardial oxidative damage. The most logical way to combat excess ROS is to use antioxidants, which have been shown to be effective in experimental studies. However, appropriate targeting delivery methods are needed for the systemic use of antioxidant-based drugs in a clinical setting. This review discusses the mechanisms of ROS generation and action in cardiac сoronary heart disease, as well as the consequences of oxidative damage. The authors present the principles of targeted antioxidant delivery using both passive and active methods involving ligands that are specific to ischaemic tissue, such as targeted homing peptides. Analysis of the results of the various studies presented in this review shows that delivery using such specific ligands may increase the bioavailability of antioxidants and the cardioprotective efficacy of drugs based on them. In the future, the use of artificial intelligence to design high-affinity targeted peptides may open new possibilities for personalized therapy for coronary heart disease. Thus, the development of targeted drug delivery systems represents one of the most promising strategies for improving the effectiveness of treatment for myocardial ischemia-reperfusion injury.

Atherosclerosis is a leading cause of morbidity and mortality globally, and neutrophils have emerged as key players in the progression and resolution of vascular inflammation. Although neutrophils are associated with atherosclerosis pathogenesis, the molecular mechanisms governing their pro- or anti-inflammatory states remain poorly defined. Here, we identify the adaptor protein TRAM as a critical molecular switch that regulates neutrophil polarization and function in atherosclerosis. Genetic deletion of TRAM in neutrophils reprograms them into a resolving phenotype, characterized by elevated levels of anti-inflammatory mediators such as Resolvin D1 (RvD1), CD200R, and SESN1, and reduced expression of pro-inflammatory mediators including leukotriene B4 (LTB4), elastase, and myeloperoxidase. Adoptive transfer of TRAM-deficient neutrophils into atherosclerotic ApoE −/− mice significantly reduces plaque size, lipid deposition, and vascular leakage, while enhancing plaque stability and improving endothelial integrity. Consistent with in vivo results, TRAM-deficient neutrophils exert protective effects on co-cultured endothelial cells in an RvD1-dependent manner. Mechanistically, TRAM deletion disrupts oxLDL-induced translocation of 5-lipoxygenase to the nuclear membrane by downregulating FLAP, which may shift lipid mediator secretion from pro-inflammatory LTB4 to pro-resolving RvD1. TRAM also functions as a stress sensor of oxLDL and free cholesterol. Furthermore, TRAM-deficient neutrophils reduce ROS generation and SYK/CaMKII signaling activation. Importantly, our scRNA-sequencing data unveil a human CD177 low neutrophil subset with low TRAM expression, mirroring the resolving phenotype of murine TRAM-deficient neutrophils. These CD177 low neutrophils exhibit reduced swarming, elastase release, and LTB4 secretion. Our findings establish TRAM as a central regulator of neutrophil plasticity and inflammation in atherosclerosis, highlighting the therapeutic potential of TRAM-targeted modulation for cardiovascular disease.

Metabolic Fluorescence Lifetime Imaging Microscopy (FLIM) algorithms have become invaluable tools for exploring deep into the complex dynamics of cellular metabolism. Monitoring subcellular parameters is of interest, particularly during photodynamic therapy (PDT), to enhance treatment efficacy. By joining together Metabolic FLIM with PLIM, it is possible to evaluate cellular metabolic states, such as oxygen consumption, redox states, pH levels, and energy production pathways. The aim of this work is to use NADH FLIM and PLIM techniques to distinguish different metabolic pattern signatures in tumor and normal cell lines using a PLIM pH sensitive complex from the family of phosphorescent [(N^C)2Ir(N^N)]+ complexes. This investigation used a combination of 2-photon (2P) excited FLIM and PLIM techniques, coupled with time-correlated single-photon counting (TCSPC) detection. All the data were collected from living cells and were analyzed through exponential fitting. For the pattern segmentation we have used the phasor plot approach. By constructing a calibration curve and simultaneously acquiring NADH-FLIM and PLIM data from our pH sensor, we were able to identify metabolic regions and distinguished different pattern signatures in tumor and normal cell lines. This combined approach provides a comprehensive view of the tumor microenvironment, offering critical insights into parameters that influence photosensitizer localization, ROS generation, and therapeutic response. By identifying metabolic and pH heterogeneity at the single-cell level, this method contributes to improving the selectivity, precision, and overall efficacy of PDT treatments.

Breast cancer remains a leading cause of mortality among women despite advances in early detection and targeted therapies, underscoring the need for safer and more effective treatment options. Drug repurposing offers a promising strategy by leveraging existing pharmacological agents with established safety profiles. Desloratadine, a second-generation H1-histamine receptor antagonist widely prescribed for allergic conditions, has attracted interest in oncology because histamine signaling influences proliferation, angiogenesis, and immune responses, yet its anticancer potential remains poorly understood. In this study, we investigated its effects in MCF-7 breast cancer cells, which harbor wild-type TP53. Desloratadine inhibited cell viability in a dose-dependent manner, with an IC50 of 14.2 µg/mL. Mechanistic analyses revealed that growth inhibition was primarily mediated through apoptosis, confirmed by Hoechst 33342 staining, ROS generation, annexin V/PI staining, and caspase-dependent pathways. Gene expression profiling demonstrated upregulation of TP53, FAS, and BAX, alongside reduced PARP-1 and NF-κB expression, with no detectable STAT3 or BCL2 expression. Flow cytometry indicated accumulation of cells in the sub-G1 phase and G2/M arrest, consistent with apoptosis induction. Molecular docking further supported these findings, showing that Desloratadine binds with high affinity to p53 (−7.0 kcal/mol), FAS (−6.8 kcal/mol), and NF-κB (−6.5 kcal/mol), forming stabilizing hydrogen bonds and hydrophobic interactions aligned with the observed gene expression changes. To confirm the functional role of TP53, we generated CRISPR-Cas9 knockout MCF-7 cells. Compared with wild-type cells, these knockout cells displayed markedly reduced sensitivity to Desloratadine, with the IC50 shifting from 14.2 µg/mL to 36.4 µg/mL, demonstrating that p53 is a key mediator of the drug’s cytotoxic effect. Collectively, these findings identify Desloratadine as a potential repurposed drug candidate for breast cancer therapy, acting at least in part through a p53-dependent apoptotic pathway.

Heptamethine cyanines are attractive NIR fluorophores for image-guided tumor phototherapy. However, most cyanines exhibit unignorably high background fluorescence, which would lead to low-contrast images in the tumor. Inspired by findings that proper modulations of cyanines can self-quench fluorescence in the aggregated state but retrieve fluorescence when they are switched to the monomer, we herein engineer four amphiphilic heptamethine cyanines (IR780-NCn, n = 3/6/12/18) with extended hydrophobic alkyl chains. By studying the optimal properties and morphology of the dyes, we finally optimize IR780-NC12 and IR780-NC18 which can form nonfluorescent nanoaggregates in PBS but disassemble and recover intense NIR emission in hydrophobic media. Upon cellular uptake, the amphiphilic cyanines show fluorescence in membranous organelles such as mitochondria (IR780-NC3 and IR780-NC6) or the cell membrane (IR780-NC12 and IR780-NC18). Also, hydrophobic shielding enhances ROS generation under laser irradiation, as observed in IR780-NC12 and IR780-NC18. In vivo, IR780-NC18 administration (i.v.) exhibits the brightest and most prolonged tumor fluorescence up to 96 h. Guided by the NIR images in the tumor, an efficient PTT/PDT antitumor effect is confirmed for IR780-NC12 and IR780-NC18 phototherapy. We believe that self-assembly tuning design is a simple and powerful strategy to develop fluorescent "turn-on" cyanines as high-contrast NIR theranostic agents to guide tumor phototherapy.

Calcium interference therapy (CIT) is a promising cancer therapeutic strategy, but its efficacy is limited by intrinsic cellular calcium regulation. To address this limitation, herein, a near-infrared (NIR)-responsive nanoplatform, UC@COFs@CaO2-HA/PAG/ICG (UCCPI), integrating dual-amplified CIT with photodynamic therapy (PDT) is engineered to enhance therapeutic outcomes. The core-shell upconversion nanoparticle-engineered covalent organic framework nanocomposites (UC@COFs) serve as both pH-dependent fluorescent probes for cancer cell imaging and drug-delivery carriers co-loading photoacid generators (PAG) and photosensitizer indocyanine green (ICG). The embedded upconversion nanoparticles (UCNPs) convert 980nm NIR light into visible emissions, enabling spatiotemporal PAG activation for localized H+ release and overcoming UV/visible light depth limitations. Surface-modified hyaluronic acid (HA)-functionalized CaO2 nanoparticles provide pH-responsive Ca2+/O2 reservoirs, facilitating CD44-mediated tumor targeting and PDT-supportive hypoxia alleviation. Crucially, NIR-triggered H+ generation simultaneously drives dual calcium amplification through accelerated CaO2 decomposition and potentiated acid-sensitive ion channel-mediated Ca2+ influx, while fueling ICG-mediated ROS generation via O2 supply for PDT. These interconnected processes synergistically amplify mitochondrial calcium overload and oxidative damage. Collectively, UCCPI demonstrates excellent biocompatibility, precise tumor targeting, and self-amplifying therapeutic effects both in vitro and in vivo. This work presents a tumor microenvironment-targeted strategy to potentiate mitochondrial dysfunction through integrated ion interference and oxidative stress mechanisms.

The β-glucan from Lentinus alleviates UVB-induced dermal fibroblasts senescence and skin photoaging.

Boosting ferroptosis therapy by sorafenib and ML385 loaded CuFe2O4 nanozymes.

Curcumin-mediated photodynamic inactivation coupled with Cu2+-catalyzed Fenton-like reaction: a cascaded antifungal strategy against Fusarium graminearum and its applications.

Photothermal-responsive curcumin-loaded copper-based nanocomposites for targeted drug release and combined immunotherapy.

Ammonium tetrathiomolybdate ameliorates heat stroke-induced murine liver injury by activating the Nrf2/HO-1 signaling pathway and inhibiting oxidative stress.

Photocatalytic chitosan films loaded with Ag-modified C-TiO2 nanohybrids for ethylene scavenging and prolonging the shelf life of bananas under visible light.

Atomically dispersed dual active sites for greatly boosting catalytically synergistic cancer therapy via ROS generation, GSH depletion and chemotherapy

DDX1 Crotonylation Mediates ACOX1 Alternative Splicing through HNRNPK to Increase Peroxisomal Oxidative Damage.

Near-infrared light-activated osmium-complex/UiO-67-bpy composite for enhanced antibacterial activity and wound healing.

Ferroptosis is newly recognized form of regular cell death which is associated with iron accumulation and lipid peroxidation in cells. This procedure leads to immense oxidative damage, inhibition of antioxidant defense, and a high generation of ROS. Ferroptosis progression is linked to mitochondrial dysfunction and p53 activation. In fact, excessive ROS generation after iron buildup leads to further mitochondrial lipid peroxidation. Curcumin, a naturally occurring polyphenolic chemical that comes from Curcuma longa, has a variety of pharmacological characteristics, such as anti-inflammatory, anti-neoplastic, and antioxidant actions. According to recent studies, curcumin and its derivatives can induce ferroptosis in cancerous cells, offering a novel means of halting tumor growth and overcoming drug resistance. Curcumin can induce ferroptosis in tumor cells via a number of regulatory mechanisms, such as those pertaining to the metabolism of iron, lipids, and amino acids. This might lead to the development of new therapeutic approaches for the treatment of cancer that is resistant to apoptosis. Ferroptosis is another way it affects anticancer immunotherapy. This study intends to demonstrate curcumin and its derivatives as strong inducers of ferroptosis and highlights their potential to transform cancer therapy paradigms by thoroughly reviewing the existing literature.

Silymarin ameliorates diet-induced gallstone formation by regulating gut microbiota-derived GCDCA to suppress ferroptosis-ROS-NFκB signaling pathway.

Breaking barriers in antimicrobial therapy: resistance mechanisms and novel antimicrobial strategies.