JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2025
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IF 9.7
Manman Xie,Canran Jiang,Cong Zhang,Yun Wu,Xiuli Zhang,Ruosi Yao,Cuiping Han,Yue Dai,Kai Xu,Shaohui Zheng
Photodynamic therapy (PDT) primarily relies on the generation of reactive oxygen species (ROS) to eliminate tumor cells. However, the elevated levels of glutathione (GSH) within tumor cells can limit the efficacy of PDT, posing a challenge to achieve complete tumor eradication. Herein, a porous iron-based metal–organic frameworks (PEG-Fe-MOFs) nanoplatform was developed for the combined application of PDT and ferroptosis in cancer treatment. The coordination between tetrakis (4-carboxyphenyl) porphyrin (TCPP) and ferric (Fe 3+ ) enabled PEG-modified Fe-MOFs (PEG-Fe-MOFs) to deliver excellent T 1 -weighted magnetic resonance (MR) imaging performance in physiological environments. Within the tumor microenvironment (TME), PEG-Fe-MOFs gradually degraded to release TCPP, which could be utilized for fluorescence imaging. Moreover, Fe 2+ enhanced intracellular ROS levels via the Fenton reaction, generating hydroxyl radicals that further amplified ROS production. This synergistic effect comprising increased ROS levels and GSH depletion augmented the efficacy of PDT while simultaneously inducing robust ferroptosis in tumor cells, thereby maximizing therapeutic outcomes. Both in vitro and in vivo experiments have demonstrated the superior T 1 weighted MR and fluorescence imaging capabilities of PEG-Fe-MOFs, along with its potent synergistic therapeutic effects on tumors. These results highlighted the potential of this nanoplatform for combining PDT and ferroptosis in cancer treatment.
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Small Science
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2025
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IF 8.3
Ximei Dai,Zhiyue Wang,Jiaqi Lu,Yutong Xu,Xingji Liu,Jianchen Qi,Tao Zheng,Feng Wang,Guangming Lu,Longjiang Zhang,Jie Sheng,Guifen Yang
Atherosclerosis (AS) is a significant contributor to cardiovascular events. Recent studies have demonstrated that ferroptosis of foam cells is a significant driver of AS. Nevertheless, insights into the precise antiferroptosis therapies remain limited. Here, a multifunctional theranostic nanoplatform is engineered by conjugating folate-modified polydopamine (PDA) nanoparticles (NPs) with L-arginine (FPLG) to inhibit ferroptosis of foam cells. In vitro studies demonstrate that FPLG NPs effectively attenuate ferroptosis in oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages by scavenging reactive oxygen species, upregulating GPX4 and NRF2 activity, and regulating lipid metabolism. In vivo, FPLG NPs exhibit preferential accumulation in atherosclerotic plaques via folate receptors (FRs)-mediated targeting and the enhanced permeability and retention effect (EPR effect), as confirmed by fluorescence imaging and chelator-free 68 Ga-labeled positron emission tomography/computed tomography (PET/CT). Treatment with FPLG NPs in ApoE −/− mice reduces plaque area by over 40%, enhances fibrous cap stability, and mitigates ferroptosis. Transcriptomics further reveals that the FPLG treatment suppresses ferroptosis and inflammatory pathways. This dual-modality platform integrates targeted ferroptosis inhibition and real-time imaging, offering a promising strategy for precise AS management.
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MICROCHEMICAL JOURNAL
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2025
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IF 5.1
Si-Ling Chen,Ming-Hua Zheng,Shao-Feng Zhang,Yu-Zhong Xie,Jing-Yi Jin
Ferroptosis, which participates in multiple pathophysiological processes, is executed by iron-dependent phospholipid peroxidation. Due to any biomolecular interaction or change resulting in modification of the local microenvironment, deep insights into these variations are indispensable for detailing ferroptosis. Mitochondria (Mito) generate reactive oxygen species (ROS) that amplify lipid peroxidation, while endosomes (Endo) take part in intracellular iron homeostasis. The two organelles are both involved in the molecular events of ferroptosis. Herein, we developed a polarity-sensitive fluorescent probe (MPY) that targeted Mito and Endo simultaneously. The polarity-triggered emission at 570 nm enables the detection of microenvironmental fluctuation. We observed a general enhancement in Mito polarity during different ferroptosis pathways. Erastin induced the most significant upregulation in Endo polarity and quantity, followed by RSL3 and FIN56, while FINO 2 induced little change. Moreover, the polarity difference between Endo and Mito varied in four ferroptosis stimuli. Accordingly, we revealed that FINO 2 could induce ferritinophagy, judged by the decreased polarity difference between Endo and Mito.
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ANALYTICAL CHEMISTRY
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2025
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IF 6.7
Lu Li,Qinglin Fei,Xuwen Sun,Qiaochun Wang,Jianhua Su,Longyun Ye,Weiding Wu,Lifang Guo
Elucidating pathway-specific ferroptosis mechanisms is crucial for advancing our understanding of cell death regulation; however, this goal has been hindered by the persistent absence of reliable detection techniques and standardized analytical approaches. Mechanistically, ferroptosis is governed by the nexus between Glutathione Peroxidase 4 (GPX4) inactivation and lipid-peroxide-driven membrane destabilization, with cysteine (Cys) as a key regulator for GPX4 synthesis and ferroptosis trigger differentiation. Lipid peroxide accumulation elevates cytoplasmic viscosity, enabling the decryption of ferroptosis-trigger mechanisms by elucidating Cys-viscosity dynamics. For this, we engineer an innovative dual-parameter sensing platform: a conformationally flexible molecular scaffold with triple-emission viscosity sensitivity was functionalized with a Cys-reactive aldehyde group. This probe system features a fluorescence quenching mechanism and then sequentially restores red and blue fluorescence in the presence of Cys and high viscosity. Notably, while distinct ferroptosis pathways induce an observable viscosity increase, the Cys flux profiles exhibit pathway-specific signatures. Direct synthesis blockade displays a remarkable Cys fluctuation (Δ[Cys] = 20%, 4 h) compared to GPX4 inhibition (Δ[Cys] = 21%, 12 h), whereas overload iron demonstrates imperceptible variation (Δ[Cys] = 28%, 36 h latency). Furthermore, the evaluation of Cys-dependent ferroptosis in pancreatic cancer models uncovers therapy response mechanisms. This work highlights the key role of Cys and viscosity kinetics in ferroptosis initiation and execution phases, advancing the fundamental research and precise regulation of ferroptosis.
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Materials Today Bio
·
2025
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IF 10.2
Langjie Chai,Jianglong Huang,Min Wang,Yihui Huang,Zhuo Huang,Ruiyu Zhang,Lu He,Haijie Wang,Danyang Chen,Yifeng Lei,Liang Guo
In chronic third-degree burn wounds, high levels of inflammatory factors such as IL-1β lead to ferroptosis in surrounding cells, thereby delaying the healing process of the burn wounds. To promote the healing of such wounds, an injectable DFO@GM-H hydrogel was developed. This hydrogel was prepared by loading deferoxamine (DFO) into gelatin microspheres (GMs), and further crosslinking in a mild reaction. The resulting DFO@GM-H hydrogels demonstrated effective self-healing and injectability, rendering them well-suited for application in irregular burn wounds. DFO@GM-H hydrogels not only maintained a moist healing environment for the burn wound healing, but also exhibited the ability to slowly release DFO, therefore overcoming the limitation of the short half-life of DFO in vivo . With sustained release and enhanced stability of DFO from the injectable hydrogels, DFO@GM-H hydrogels demonstrated excellent biocompatibility, effectively promoted cell proliferation, migration and angiogenesis, showed antibacterial activity, and effectively inhibited cellular ferroptosis both in vitro and in vivo . Consequently, DFO@GM-H hydrogels accelerated the healing of burn wounds in rats via ferroptosis inhibition and enhanced cellular response. Therefore, DFO@GM-H hydrogel is anticipated to emerge as a novel bioactive dressing for the management of burn wounds.
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Scientific Reports
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2025
·Vol. 15
·期 1
·1-14
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IF 3.9
Zhang Yuxi,Zhan Junbiao,Qiu Zhen,Tian Hao,Lei Shaoqing,Huang Qin,Xue Rui,Sun Qian,Xia Zhongyuan
Myocardial cold ischemia/reperfusion (I/R) injury is an inevitable consequence of heart transplantation, significantly affecting survival rates and therapeutic outcomes. Growth Differentiation Factor 15 (GDF15) has been shown to regulate GPX4-mediated ferroptosis, playing a critical role in mitigating I/R injury. Meanwhile, verbascoside (VB), an active compound extracted from the herbaceous plant, has demonstrated myocardial protective effects. In this study, heart transplantation was performed using a modified non-suture cuff technique, with VB administered at a dose of 20 mg/kg/day via intraperitoneal injection for 3 days in vivo. In vitro, cardiomyocytes were pretreated with 50 µg/ml VB for 24 h. VB treatment significantly reduced histopathological injury, decreased myocardial injury markers, and inhibited ferroptosis and oxidative stress during myocardial cold I/R injury in vivo. In vitro experiments further demonstrated that GDF15 alleviates ferroptosis induced by hypoxic reoxygenation by upregulating GPX4. Therefore, it is concluded that VB preconditioning can effectively reduce ferroptosis induced by myocardial cold I/R after heterotopic heart transplantation, possibly through up-regulation of GDF15/GPX4/SLC7A11 pathway.
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ACS Applied Materials & Interfaces
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2025
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IF 8.2
Benyan Zheng,Hongjie Zhang,Gaoyuan Yu,Rui Geng,Yanxiang Sang,Guimin Huang,Xuechun Wang,Jing Wang,Yuan Hu,Xiaopeng Ma
Nanozyme-mediated nanocatalytic therapy, by mimicking the activity of redox enzymes, generates highly toxic reactive oxygen species (ROS) within tumor cells, thereby opening a pathway for tumor-specific therapy. However, achieving satisfactory therapeutic outcomes with nanozymes remains challenging due to the inherent complexity of the tumor microenvironment (TME). In this context, we designed a two-dimensional layered double hydroxide (LDH) nanozyme loaded with Au nanoparticles, while incorporating bioactive Ca2+ and Fe3+ ions (denoted as MgCaFe-LDH@Au NSs) to target the specific needs of the TME. The designed nanozyme mimics glucose oxidase to facilitate self-sufficient H2O2 production and simulates catalase and glutathione peroxidase to overcome the adverse conditions of hypoxia and elevated GSH levels in the TME. Subsequently, the nanozyme emulates peroxidase activity to generate ROS, amplifying oxidative stress and causing redox imbalance, ultimately inducing ferroptosis in tumor cells. Moreover, MgCaFe-LDH@Au NSs also function as an inorganic semiconductor sonosensitizer with a tunable band structure, enabling the generation of abundant ROS under ultrasound irradiation to achieve synergistic sonodynamic and catalytic therapy. Notably, the high levels of ROS induced by the nanozyme, along with the interference in tumor ATP synthesis, enhanced the calcium overload in the TME caused by the release of Ca2+ from the nanozyme. In summary, this two-dimensional nanomaterial, through nanozyme and ultrasound-catalyzed synergistic disruption of tumor energy supply and redox balance, exhibited significant therapeutic efficacy in a 4T1 tumor-bearing mouse model. This study also highlights the immense potential of multimetal LDHs as inducers of calcium overload and ferroptosis in tumor therapy.
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FREE RADICAL BIOLOGY AND MEDICINE
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2020
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IF 6.17
Tao Bai,Mingxing Li,Yuanfeng Liu,Zhentao Qiao,Zhiwei Wang
Atherosclerosis (AS) is the fundamental pathological state of many serious vascular diseases, characterized by disorders of lipid metabolism . Ferroptosis is a type of regulated cell death that is mainly mediated by iron-dependent lipid peroxidation . In this study, whether ferroptosis has occurred in AS and the potential effects of ferroptosis on AS were investigated. Ferroptosis inhibitor ferrostatin-1 (Fer-1) was administered to high-fat diet (HFD)-induced AS in ApoE −/- mice. The results showed that Fer-1 could alleviate AS lesion in HFD-fed ApoE −/- mice. Additionally, Fer-1 partially inhibited the iron accumulation, lipid peroxidation and reversed the expressions of ferroptosis indicators SLC7A11 and glutathione peroxidase 4 (GPX4) in HFD-fed ApoE −/- mice. Next, we evaluated the effects of inhibition of ferroptosis on oxidized-low density lipoprotein (ox-LDL)-induced mouse aortic endothelial cells (MAECs). Results showed that Fer-1 increased cell viability and reduced cell death in ox-LDL-treated MAECs. Moreover, Fer-1 decreased iron content and lipid peroxidation and up-regulated the levels of SLC7A11 and GPX4. Additionally, Fer-1 down-regulated the expressions of adhesion molecules and up-regulated eNOS expression. Iron chelator deferoxamine was used to demonstrate ferroptosis could be partially inhibited by iron complexation in ox-LDL-treated MAECs. Our results indicated that ferroptosis might occur during the initiation and development of AS. More importantly, inhibition of ferroptosis could alleviate AS through attenuating lipid peroxidation and endothelial dysfunction in AECs. Our findings might contribute to a deeper understanding regarding the pathological process of AS and provide a therapeutic target for AS.
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Frontiers in Pharmacology
·
2025
·
IF 4.8
Junhui Yu,Ningning Shao,Jianming Yang,Long Yang,Kaiwen Hong,Yuzhu Chen,Xiaoming Zhao,Hongzhi Yu,Tao Zhang,Jinrui Dong
Introduction Nonalcoholic steatohepatitis (NASH) is a chronic liver disease associated with oxidative stress and ferroptosis, leading to liver injury and fibrosis. Garlic, renowned for its antioxidant and hepatoprotective properties, is commonly used in traditional medicine. Ultrafine powder technology enhances the physicochemical properties of natural products, improving their bioavailability and efficacy. This study explores the protective effects of ultrafine garlic powder (UGP) on NASH and its underlying mechanisms. Methods In this study, UGP was prepared by high-speed particle collision technology and compared with traditional garlic powder (TGP). Results UGP exhibited a particle size (d(0.5) of approximately 4 μm) that is 30 times smaller than TGP, showing significantly smaller particle size and lower contact angle (UGP=59.775°vs TGP=83.545°). UGP also demonstrated improved solubility and dispersibility, along with an enrichment of key organosulfur compounds such as allicinAllicin, Alliin, SAC, and GSAC. In vitro, UGP significantly reduced palmitic acid-induced ROS production (n=4, p< 0.0001), prevented mitochondrial dysfunction (n=4, p=0.0035), and thereby reduced hepatic stellate cell activation. UGP lowered intracellular Fe2+ levels in hepatocytes from 68.72% to 34.48% (n=4) and significantly protected hepatocytes from erastin-induced ferroptosis (cell viability: UGP treatment 23.46% vs erastin stimulation 53.91%, n = 4, p <0.0001).In the acute liver fibrosis model induced by methionine- and choline-deficient diet supplemented with 60 kcal% fat (CDHF), UGP significantly improved liver histology. Compared to the model group, the liver/body weight ratio of mice was significantly restored (n=4, p<0.0001), and histopathological staining showed a substantial improvement in liver damage. Biochemically, UGP significantly reduced the levels of liver collagen, triglycerides, and cholesterol (n = 6, p < 0.0001). Fibrosis-related mRNA and pro-inflammatory mRNA expression were significantly decreased. Western blot results showed that UGP significantly inhibited the activation of p-ERK signaling. In the chronic liver fibrosis model induced by a diet with 60 kcal% fat (HFD), UGP demonstrated similar therapeutic effects. RNA-seq analysis revealed that UGP modulated key pathways, including fatty acid metabolism and the MAPK signaling pathway, and suppressed ROS production, further highlighting its therapeutic potential in NASH treatment. Discussion Taken together, these data suggest that UGP alleviates NASH by inhibiting hepatocyte ferroptosis and modulating ERK-dependent oxidative stress, supporting its potential as a therapeutic agent.
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KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
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2025
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IF 3.1
Rui-Shi Wei,Yong-Ping Liu,Chun-Dong Gu,Shi-Lei Zhao,Li Feng,Jian-Rong Yu
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with a 5-year survival rate of less than 20% and a high risk of recurrence despite advances in treatment. This study aimed to identify new therapeutic targets to increase the effectiveness of NSCLC treatments. We examined the role of USP54 in ferroptosis using an MTT assay and assessed the levels of reactive oxygen species (ROS), ferrous iron (Fe 2+ ), and malondialdehyde (MDA). To explore the underlying molecular mechanism, the intermolecular interactions was assessed using coimmunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays. We found that USP54 expression was reduced in NSCLC and that its overexpression inhibited NSCLC cell proliferation while inducing ferroptosis, as indicated by increased ROS, Fe 2+ , and MDA levels, along with changes in SLC7A11, GPX4, and ACSL4 expression. Additionally, USP54 mediated the deubiquitination of FOXA2, decreasing its degradation. And FOXA2 promoted ACSL4 transcription, which further induced ferroptosis in NSCLC cells. In conclusion, USP54 promotes ferroptosis and inhibits NSCLC progression by stabilizing FOXA2, which in turn activates ACSL4 transcription. This study provides a theoretical foundation for the development of therapies targeting USP54 or ACSL4 for NSCLC treatment.
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ACS Applied Nano Materials
·
2025
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IF 5.5
Lin Li,Tiantian Lei,Kejing Wang,Yong Liu,Bingjun Sun,Lin Chen
Chemotherapy has been established as a standard therapeutic regimen for triple-negative breast cancer (TNBC). However, the efficacy of current therapeutic approaches remains suboptimal, primarily attributed to insufficient drug accumulation and the rapid development of chemoresistance. Thus, the rational design of drug delivery systems capable of triggering multimodal cell death pathways represents a promising strategy to combat TNBC. Ferroptosis emerges as a potent form of nonapoptotic cell death, showing great potential for tumor inhibition. The effective codelivery of chemotherapeutic drugs and ferroptosis activators provides potential ideas for the treatment of TNBC. Prodrug-based nanoassemblies have attracted tremendous attention in drug delivery, especially homodimeric prodrugs with ultrahigh drug loading. However, due to their symmetric structures, most homodimeric prodrugs exhibit poor self-assembly ability. Herein, two doxorubicin (DOX) homodimeric prodrugs were designed and coassembled with a GPX4 inhibitor (ML210). The incorporation of ML210 significantly promotes the stability of DOX nanoassemblies and improves the intracellular breakage of the DOX prodrug by regulating the GSH level. As a result, the ML210-driven doxorubicin homodimeric prodrug nanoassemblies exhibit high drug loading capacity, high self-assembly stability, and synergistic chemotherapy-ferroptosis effects. Our results present a viable approach to promote the self-assembly of homodimeric prodrugs while offering an efficient nanoplatform for TNBC treatment.
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JOURNAL OF NANOBIOTECHNOLOGY
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2025
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IF 12.6
Zheng Xiao,Peng Luo,Guoli Li,Huifang Tan,Chen Zhou,Dong Zeng,Yinyin Chen,Ying Li
Background: Renal interstitial fibrosis (RIF) is a hallmark pathological process in the progression of chronic kidney disease (CKD). However, effective therapies to halt or reverse RIF remain limited. Emerging evidence implicates ferroptosis as a critical contributor to RIF. Rosiglitazone (Rosi), a widely used thiazolidinedione, exhibits anti-ferroptotic activity but suffers from poor aqueous solubility, limited renal specificity, and systemic side effects. Results: Here, we constructed a renal tubular epithelial cell-targeted nano-based drug delivery system-Rosi-loaded, K3 peptide-modified, PEGylated hollow polydopamine(HPDA) nanoparticles (Rosi@HPDA-PEG-K3 NPs). This system displayed excellent biocompatibility and lesion-specific targeting, achieving prolonged retention in fibrotic kidneys. The in vitro and in vivo experiment demonstrated that this nano-based drug delivery system inhibited ferroptosis through downregulation of ACSL4, iron ion chelation, and ROS scavenging. Concurrently, it stabilized mitochondrial membrane potential and synergistically suppressed inflammatory responses, ultimately attenuating RIF. Conclusions: In summary, Rosi@HPDA-PEG-K3 NPs deliver Rosi specifically to renal renal tubular epithelial cells(TECs)and exert an anti-RIF effect through the integration of ferroptosis inhibition, mitochondrial protection, and inflammation modulation. Our study establishes a nanotherapeutic platform with precise targeting and multifunctional efficacy, highlighting its scientific rigor and the clinical translational potential of RIF.
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