Advanced Science
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2026
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IF 14.1
Zimei Wu,Yan Xu,Lang Qin,Zemin Ling,Yingjie Mai,Xiong Tian Guo,Jiajia Chen,Leping Yan,Lin Wang,Liming Bian,Fuxin Wei
Intervertebral disc degeneration (IVDD) is driven by persistent inflammation–oxidative stress that disrupts annulus fibrosus (AF) homeostasis. Guided by network pharmacology and docking, we prioritized the NF-κB–LCN2 axis as a druggable target of wedelolactone (WDL). To achieve targeted modulation, we engineered a dual-network ROS-responsive hydrogel (WPG) in which a phenylboronic-ester/PVA redox-cleavable network interpenetrates a covalently crosslinked GelMA–elastin matrix, enabling mechanically robust yet stimulus-triggered WDL release. WDL suppressed NF-κB activation and downregulated LCN2 in both macrophages and AF cells. Conditioned-medium co-culture demonstrated that WDL disrupts macrophage-derived LCN2-mediated paracrine amplification, breaking the self-sustaining inflammatory loop. Bulk RNA-seq across both cell types revealed coordinated downregulation of NF-κB – driven chemokine cascades and restoration of adhesion and ECM gene programs following WPG treatment. In a rat AF-defect model, intradiscal WPG administration preserved disc height and T 2 -weighted MRI signal, reduced MMP13 while increasing Collagen I and Aggrecan expression, suppressed nuclear P-p65 and LCN2, and improved segment biomechanics—without eliciting adverse hematological or organ responses. Collectively, these findings establish that aligning molecular targeting (NF-κB–LCN2 modulation) with the pathophysiological context via ROS-gated delivery provides a synergistic strategy for AF repair and attenuation of IVDD progression.
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高影响因子
Theranostics
·
2026
·Vol. 16
·期 3
·1281
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IF 13.3
Jiayi Hu,Xiaoyi Bao,Meihua Ting,Yecheng Tao,Ran Li,Guosheng Fu,Fuyu Qiu,Jing Zhao,Wenbin Zhang
Rationale: Myocardial ischemia-reperfusion injury (MIRI) poses a critical clinical challenge due to intertwined oxidative stress and cuproptosis-driven cell death. Current therapies inadequately address dual-pathology mechanisms (ROS overproduction and copper dysregulation), while conventional drug delivery lacks spatiotemporal precision. Methods: A ROS-responsive hydrogel (OD@G4CAsi-FDX1) was engineered via dynamic Schiff base crosslinking between oxidized dextran (OD) and polyamidoamine dendrimers (PAMAM G4). The hydrogel co-encapsulates antioxidant caffeic acid (CA) and FDX1-targeted siRNA (si-FDX1). In vitro biocompatibility, ROS scavenging, and mitochondrial protection were assessed in primary cardiomyocytes. In vivo efficacy was evaluated in a murine MIRI model following intramyocardial hydrogel injection. Cardiac function, infarct size, and molecular markers were analyzed. Results: In vitro , it reduced ROS, preserved mitochondrial membrane potential, and suppressed pro-inflammatory cytokines. In vivo , it reduced infarct size, suppressed cuproptosis markers, and improved cardiac function. Mechanistically, si-FDX1 blocked DLAT oligomerization, while CA neutralized ROS, synergistically restoring redox homeostasis. This efficacy was enabled by sustained ROS-triggered release. Conclusions: OD@G4CAsi-FDX1 hydrogel dual-targets ROS and cuproptosis via a single injectable platform, overcoming limitations of conventional mono-mechanistic therapies. It demonstrates significant cardioprotection and clinical potential for MIRI management.
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Pharmaceutics
·
2026
·Vol. 18
·期 1
·98
·
IF 5.5
Jingjing Wang,Rui Ni,Ziwei Li,Jianhong Chen,Yao Liu
Background/Objectives:Wound healing represents a pervasive and urgent clinical challenge. Hard-to-heal chronic wounds are frequently complicated by infections, inflammatory responses, and oxidative stress. Currently, wound dressings are broadly categorized into dry and moist types, with moist wound dressings for chronic wounds accounting for approximately 70% of market revenue. Recently, adipose-derived stem cells (ADSCs), which possess self-renewal and multi-lineage differentiation capabilities, have emerged as a promising strategy for promoting tissue regeneration and wound repair.Methods:In this study, we developed a novel luteolin nanoparticle–ADSCs composite hydrogel (GelCA@LUT@ADSCs). This system was constructed by first encapsulating ADSCs within a chitosan/alginate hydrogel (GelCA), followed by coating the hydrogel with luteolin-loaded nanoparticles (LUT@NPs).Results:The sustained release of LUT@NPs from the hydrogel modulates the wound microenvironment, enhancing the pro-healing functions of ADSCs at the wound site. The GelCA hydrogel exhibited excellent biocompatibility. Both in vitro and in vivo results demonstrated that GelCA@LUT@ADSCs treatment effectively reduced inflammation, promoted angiogenesis and collagen deposition, stimulated cell proliferation and migration, and polarized macrophages toward an anti-inflammatory, pro-healing M2phenotype, thereby accelerating wound healing.Conclusions:Overall, this innovative therapeutic approach provides a novel strategy for wound management through a synergistic division of labor between pharmaceutical agents and stem cells.
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Materials Today Bio
·
2026
·
IF 10.2
Jialei Luo,Xinyi Yan,Kang Fu,Yuxuan Qiu,Yana Xu,Zhaojie Wang,Xuexiao Li,Ting Lin,Ying Wang,Yunting Zhang,Yawei Yu,Shibo Wang,Jianqing Gao,Gaoyi Yang
Diabetic wounds represent a common and challenging complication of diabetes mellitus, characterized by a complex pathological microenvironment that includes excessive reactive oxygen species (ROS), chronic inflammation, hypoxia, and impaired nitric oxide (NO) synthesis. These factors collectively contribute to delayed wound healing, increased infection risk, and potential progression to chronic non-healing ulcers. Herein, we constructed a multifunctional injectable hydrogel (Prussian blue nanozyme and S-nitrosothiol-loaded hydrogel, PBE&SNO@HG) co-loaded with multi-enzyme-mimicking Prussian blue nanozymes (PBE) and an ultrasound-responsive nitric oxide (NO) donor (SNO). This composite hydrogel exhibited favorable injectability and tissue adhesiveness. The incorporated PBE nanozymes simultaneously mimicked superoxide dismutase (SOD) and catalase (CAT), enabling the scavenging of superoxide anions (⋅O 2 - ) and hydrogen peroxide (H 2 O 2 ), thereby reducing oxidative stress levels at the wound site. Additionally, the ultrasound (US)-responsive release of NO promoted angiogenesis and alleviates inflammatory responses in the wound area. Animal experiments demonstrated that this hydrogel system significantly enhances collagen deposition, accelerates re-epithelialization, promotes hair follicle regeneration, and accelerates wound healing. This study demonstrated the synergistic effect of combining antioxidant strategies with gas therapy in diabetic wound treatment, while also indicating that US-responsive hydrogel materials can achieve on-demand release of therapeutic molecules via external field stimulation, thereby providing a novel strategy for chronic wound management.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2026
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IF 3.6
Simin Yang,Ranting Zhao,Li Lei,Xiangbo An,Jiangli Xu,Han Xu,Jiahui Wang,Han Xiao,Youyi Zhang,Xiaoda Yang,Siwang Yu
While exercise is well-established as a protective strategy against non-alcoholic fatty liver disease, its role in acute liver injury (ALI) remains poorly understood. Nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of antioxidant response element (ARE)-dependent gene expression, plays an important role in the pathogenesis of liver diseases, where oxidative stress contributes significantly to both chronic progression and acute injury. This study investigated whether exercise confers protection against ALI via the Nrf2 signaling pathway and elucidated the underlying molecular mechanisms. We found that acute treadmill exercise time- and intensity-dependently activated hepatic Nrf2 signaling in mouse, conferring significant protection against ALI induced by alcohol, acetaminophen, or carbon tetrachloride. Conversely, exercise failed to protect against and even exacerbated ALI in Nrf2-deficient mice. Furthermore, using antioxidant Trolox and AMPKα2-knockout mice, we demonstrated that exercise activated hepatic Nrf2 primarily via ROS and AMPK signaling. Additionally, we identified exercise-induced elevation of epinephrine as a novel mechanism for activating hepatic Nrf2. In conclusion, our study demonstrates that exercise protects against ALI by activating the hepatic Nrf2/ARE signaling axis and delineates the associated molecular mechanisms, providing a scientific rationale for exercise-based therapeutic interventions.
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JOURNAL OF NANOPARTICLE RESEARCH
·
2026
·Vol. 28
·期 6
·139
·
IF 3.5
Luo Haoyu,Liu Feng,Li Jiale,Wang Tao,Lv Lianpeng,Wang Bing
Reactive oxygen species (ROS)-mediated therapeutic modalities, including photodynamic therapy (PDT) and copper ion-mediated chemodynamic therapy (CDT), have been recognized as highly promising non-invasive strategies for cancer treatment. However, their therapeutic efficacy is frequently restricted by poor subcellular targeting capability. To address this challenge, a mitochondria-targeted nanoplatform (Cu@GO-PEG-Ce6/TPP) was developed for light-triggered ROS therapy. Driven by triphenylphosphine (TPP) moieties, selective accumulation of the nanoplatform within mitochondria was achieved. Upon single 660 nm laser irradiation, singlet oxygen ( 1 O 2 ) was generated by the photosensitizer Ce6 to execute the PDT effect, while the loaded copper ions catalyzed endogenous H 2 O 2 within tumor cells through a Fenton-like reaction, leading to in situ production of highly toxic hydroxyl radicals (•OH) to fulfill the CDT function. Additionally, mild photothermal effect (PTT) was produced by the graphene oxide scaffold, with a photothermal conversion efficiency of 22.48%, through which the Fenton-like reaction rate was thermodynamically accelerated, thereby achieving synergistic PTT–CDT enhancement. The combination of mitochondrial localization and mild hyperthermia triggered an amplified local ROS burst. In vitro cellular experiments demonstrated that, under 660 nm laser irradiation at 0.5 W/cm 2 , a tumor cell killing rate of 75.89% was achieved through PDT/CDT/PTT trimodal synergistic effects, and cancer cell apoptosis was significantly enhanced. Consequently, this work provides a novel strategy for precision cancer therapy by co-localizing ROS generation and mild hyperthermia at the most vulnerable subcellular site.
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JOURNAL OF DRUG TARGETING
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2026
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IF 4.7
Jingjing Hu,Ke Chen,Yang Chen,Hua Yin
Hepatocellular carcinoma (HCC) is highly aggressive and chemoresistant, severely limiting the clinical efficacy of current therapies. Methyltransferase-like 3 (METTL3), a key regulator of N6-adenosine methylation (m6A), is overexpressed in HCC and promotes its malignant progression, serving as a promising therapeutic target. siMETTL3 can specifically silence METTL3 but suffers from poor in vivo stability, nuclease degradation, and low delivery efficiency, hindering its clinical translation. To address these issues, we developed a reactive oxygen species (ROS)-responsive nanocarrier termed PEI-PBA-BSA for efficient siMETTL3 delivery, and systematically evaluated its physicochemical properties, tumour-targeting ability, and anti-HCC efficacy. Our results demonstrated that the nanocarrier encapsulated and protected siMETTL3. Through enhanced cellular uptake and ROS-triggered controlled release in the tumour microenvironment (TME), this nanocarrier efficiently silenced METTL3. In vitro, the nanoparticles significantly inhibited hepatoma cell proliferation, migration, invasion, and stemness. In vivo, the nanoparticles effectively suppressed tumour growth (with a tumour inhibition rate of up to 68%) and demonstrated good biosafety. In summary, PEI-PBA-BSA@siMETTL3 (PPB@siM3) represents a promising nanoplatform that mediates targeted and controlled siRNA release via TME-specific ROS responsiveness, overcoming core bottlenecks in traditional METTL3 gene therapy.
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Acta Pharmaceutica Sinica B
·
2026
·
IF 14.6
Xiayun Chen,Ziqi Liang,Lichong Lu,Zhouchuan Shao,Wenhui Tang,Yiqi Liu,Jianqiao Li,Baizhong Chen,Enping Lai,Guodong Zheng,Minyan Wei,Shiying Li
Drug-induced liver injury (DILI) is a predominant cause of acute liver failure, intricately associated with excessive reactive oxygen species (ROS) production and the activation of inflammatory cascades. In this study, a metal–drug coordinated nanozyme (M-dCNs) is rationally designed to simultaneously scavenge ROS and polarize Kupffer cells to alleviate DILI. Specifically, the coordination between ferric ions (Fe 3+ ) and the complementary therapeutic agents of hesperetin (HST) and KPLH (KPLH1130) facilitates the formation of M-dCNs with uniform particle distribution and enhances structural stability. Notably, M-dCNs exhibits intrinsic antioxidant enzyme-mimetic activity, efficiently neutralizing intracellular ROS in damaged hepatocytes and thereby disrupting apoptosis-related signaling pathways. In parallel, M-dCNs synergistically reprograms hepatic macrophages toward an anti-inflammatory phenotype, leading to a marked reduction in pro-inflammatory cytokines such as tumor necrosis factor α (TNF- α ) and interleukin 1 β (IL-1 β ), and ultimately suppressing inflammatory cascades. In vivo studies demonstrate the hepatoprotective potential and therapeutic efficacy of M-dCNs in attenuating oxidative stress, reducing inflammatory cell infiltration, and restoring liver function. Collectively, this work presents a promising strategy for the treatment of DILI via the concurrent modulation of redox homeostasis and inflammatory microenvironment.
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ACS Applied Materials & Interfaces
·
2026
·
IF 7.8
Congshu Feng,Jiaxin Wu,Zilong Chen,Jinghang Li,Xinyang Deng,Wei Wang,Lesan Yan
Tumor cell survival and progression are critically dependent on intracellular redox homeostasis, with mitochondria playing a central role in maintaining this balance via antioxidant defenses. Consequently, therapeutic strategies that target mitochondrial function to disrupt this delicate balance are attracting increasing attention. Natural pro-oxidant drugs exhibit unique biological activities and relatively low systemic toxicity, demonstrating considerable promise compared to conventional chemotherapeutic agents. However, their clinical translation is impeded by poor solubility, rapid clearance, and limited tumor penetration. To overcome these limitations, this study designed a reactive oxygen species (ROS)-responsive amphiphilic block prodrug copolymer (PCC), which was synthesized via polycondensation of a cinnamaldehyde (CA)-functionalized ROS-cleavable thioketal monomer (TCA) with curcumin (Cur) and mPEG. This design enables the codelivery of CA and Cur. The self-assembled PCC nanoparticles demonstrated favorable biocompatibility and high drug delivery efficiency. In vitro, PCC NPs were effectively internalized by 4T1 tumor cells, where they rapidly and continuously released CA and Cur upon intracellular ROS stimulation. The two agents acted synergistically to promote ROS generation, induce calcium ion overload, and reduce mitochondrial membrane potential. This process established a positive feedback loop that amplified oxidative stress, disrupted the redox homeostasis of tumor cells, and ultimately induced apoptosis. Compared with free CA and Cur, PCC exhibited significantly cytotoxicity against 4T1 cells with the half-inhibitory concentration (IC50) of 13.93 μM, which is markedly lower than the 21.66 μM for free Cur and 193.06 μM for free CA. In vivo experiments confirmed that PCC nanoparticles could accumulate at tumor sites via the enhanced permeability and retention (EPR) effect, achieving a tumor inhibition rate of up to 86% and significantly suppressing tumor growth compared to other experimental groups. This work constructs an intelligent delivery platform based on a ROS-responsive drug delivery system, offering a promising strategy for the efficient delivery of natural antitumor drugs.
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Frontiers in Chemistry
·
2023
·
IF 5.5
Chang Yongliang,Wu Xiawei,Lu Shengwei,Du Jiahao,Long Yixiu,Zhu Yefei,Qin Huanlong
Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory bowel disease characterized by inflammation, intestinal barrier injury, and imbalance of gut microbiota. Excess accumulation of reactive oxygen species (ROS) is closely correlated with the development and reoccurrence of IBD. Previous researches demonstrate that procyanidin, as a natural antioxidant, exhibits strong ability of eliminating ROS, thus showing good therapeutic effects in the inflammation-related diseases. Non-etheless, its poor stability and solubility always limits the therapeutic outcomes. Here, we typically designed an antioxidant coordination polymer nanoparticle using the engineering of procyanidin (Pc) and free iron (Fe), named Pc-Fe nanozyme, for effectively scavenging ROS and further inhibiting inflammation while altering the gut microbiome for the treatment of colitis. Furthermore, in vitro experiments uncover that Pc-Fe nanoparticles exert strong multi biomimic activities, including peroxidase, and glutathione peroxidase, for the scavenging of ROS and protecting cells from oxidative injury. In addition, the colon accumulation of Pc-Fe nanozyme effectively protects the intestinal mucosa from oxidative damage while significantly downregulates pro-inflammatory factors, repairs the intestinal barriers and alternates gut microbiome after orally administrated in sodium dextran sulfate (DSS) induced colitis mice. The results collectively illustrate that the multienzyme mimicking Pc-Fe nanozyme owns high potential for treating IBD through scavenging ROS, inhibiting inflammation, repairing gut barriers and alternating gut microbiome, which further promising its clinical translation on IBD treatment and other ROS induced intestinal diseases.
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JOURNAL OF HAZARDOUS MATERIALS
·
2023
·
IF 13.6
Mukhtiar Ali,Xin Song,Qing Wang,Zhuanxia Zhang,Meng Zhang,Xing Chen,Zhiwen Tang,Xin Liu
In this study, a set of comprehensive experiments were conducted to explore the effects of temperature on the biodegradation, bioavailability , and generation of reactive oxygen species (ROS) by thermally enhanced biodegradation (TEB) under benzene and BaP co-contaminated conditions. The biodegradation rates of benzene increased from 57.4% to 88.7% and 84.9%, and the biodegradation efficiency of BaP was enhanced from 15.8% to 34.6% and 28.6%, when the temperature was raised from the ambient temperature of 15 °C to 45 °C and 30 °C, respectively. In addition, the bioavailability analysis results demonstrated that the water- and butanol-extractable BaP increased with elevated temperatures. High enzymatic activities and PAH-RHD α gene in gram-positive bacteria favored the long-term elevated temperatures (30 and 45 °C) compared to gram-negative bacteria. Moreover, ROS species (O 2 •− and •OH) generation was detected which were scavenged by the increased superoxide dismutase and catalase activities at elevated temperatures. Soil properties (pH, TOC , moisture, total iron, Fe 3+ , and Fe 2+ ) were affected by the temperature treatments, revealing that metal-organic-associated reactions occurred during the TEB of benzene–BaP co-contamination. The results concluded that biodegradation of benzene–BaP co-contamination was greatly improved at 45 °C and that microbial activities enhanced the biodegradation under TEB via the increased bioavailability and generation and degradation of ROS.
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Advanced Healthcare Materials
·
2023
·
IF 10
Qing Yao,Yingying Tang,Sheng Dai,Lihui Huang,Zewei Jiang,Shiming Zheng,Meng Sun,Yitianhe Xu,Ruijie Lu,Tuyue Sun,Huirong Huang,Xinyu Jiang,Xiaomin Yao,Guangyong Lin,Longfa Kou,Ruijie Chen
Acute liver failure (ALF) is a severe liver disease caused by many reasons. One of them is the overdosed acetaminophen (APAP), which is metabolized into N -acetyl-p-benzoquinone imine (NAPQI), an excessive toxic metabolite, by CYP2E1, resulting in excessive reactive oxygen species (ROS), exhausted glutathione (GSH), and thereafter hepatocyte necrosis. N -acetylcysteine is the Food and Drug Administration-approved drug for detoxification of APAP, but it has limited clinical application due to the short therapeutic time window and concentration-related adverse effects. In this study, a carrier-free and bilirubin dotted nanoparticle (B/BG@N) is developed, which is formed using bilirubin and 18 β -Glycyrrhetinic acid, and bovine serum albumin (BSA) is then adsorbed to mimic the in vivo behavior of the conjugated bilirubin for hitchhiking. The results demonstrate that B/BG@N can effectively reduce the production of NAPQI as well as exhibit antioxidant effects against intracellular oxidative stress via regulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signal axis and reducing the production of inflammatory factors. In vivo study shows that B/BG@N can effectively improve the clinical symptom of the mice model. This study suggests that B/BG@N own increases circulation half-life, improves accumulation in the liver, and dual detoxification, providing a promising strategy for clinical ALF treatment.
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