ACS Applied Materials & Interfaces
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2026
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IF 7.8
Zijia Jiang,Yifan Zhao,Zequn Li,Huimei Jiang,Bai Lv,Jie Cao
Photodynamic therapy (PDT) faces significant challenges in clinical applications, including tumor hypoxia, the poor water solubility of photosensitizers, and insufficient targeting specificity. To address these limitations, we developed a biomimetic nanoagonist, 4T1@MFCB, by coloading a near-infrared photosensitizer (CyI) and a GLUT1 inhibitor (BAY-876) into a manganese/iron bimetallic metal–organic framework (MOF), followed by coating with the homologous 4T1 cell membrane. The manganese component catalyzes the decomposition of endogenous H2O2 to generate oxygen, alleviating tumor hypoxia and enhancing PDT efficacy, while the iron component promotes ferroptosis via the Fenton reaction. Meanwhile, BAY-876 inhibits glucose uptake, disrupting NADPH production and the cystine-to-cysteine reduction process, which leads to cystine accumulation and glutathione (GSH) depletion. These effects collectively suppress the Solute Carrier Family 7 Member 11(SLC7A11)/glutathione (GSH)/glutathione peroxidase 4 (GPX4) antioxidant axis, thereby triggering disulfidptosis. Under near-infrared irradiation, CyI mediates effective photodynamic and photothermal therapy (PTT). Both in vitro and in vivo studies demonstrate that 4T1@MFCB enables synergistic PDT/ferroptosis/disulfidptosis therapy, significantly inhibiting tumor growth without obvious systemic toxicity. This work highlights a multimodal treatment strategy that integrates metabolic intervention with nanocatalytic therapy, providing a promising approach for the precision treatment of hypoxic and therapy-resistant tumors.
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PubMed
高影响因子
PHYTOMEDICINE
·
2025
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IF 8.3
Shaowei Zheng,Ya Gao,Houkang Cao,Kai Guo,Wenxiu Wang,Guiying Lu,Shasha Wang,Mingli Zhong,Bo Li,Kefeng Zhang,Riming Wei,Jianzhao Wu
Background Acute liver failure (ALF) is associated with ferroptosis and currently lacks specific drugs and therapies. Previous studies have shown the hepatoprotective activity of Sophoricoside (SOP) in diverse models of hepatic injury. However, the role of SOP in ALF caused by lipopolysaccharide (LPS)/D-galactosamine (D-GalN) is still unknown. Purpose To investigate the therapeutic effects of SOP on ALF and its underlying mechanisms of action. Methods In vivo , an ALF mouse model was established using LPS and D-GalN. RNA sequencing was used to identify differentially expressed genes, which were subsequently confirmed by Western blot and qRT-PCR. In vitro , erastin was used to induce ferroptosis in HepG2 cells. Subsequently, the cells were treated with SOP, the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385, and the glutathione peroxidase 4 (GPX4) inhibitor RSL3. Additionally, siRNA was utilized for Nrf2 knockdown. Measurements of biochemical markers, reactive oxygen species (ROS) levels, alterations in mitochondrial membrane potential, qRT-PCR, and Western blot analysis were used to confirm the effectiveness and mechanism of SOP. Finally, the interaction between SOP and Nrf2 was verified through molecular docking, surface plasmon resonance (SPR), and cellular thermal shift assay (CETSA). Results In vivo , experimental analysis revealed that SOP ameliorated liver injury, hepatocyte Fe 2+ accumulation, and oxidative stress. RNA sequencing analysis indicated that SOP reversed the abnormal expression of genes related to Nrf2 and the ferroptosis pathway. In vitro , SOP ameliorated erastin-induced oxidative stress, ROS accumulation, and mitochondrial membrane potential loss. After the application of pharmacological inhibitors and siRNA knockdown, the SOP’s inhibitory effect on ferroptosis was antagonized. Conclusion SOP alleviated ALF by activating the Nrf2/GPX4 signaling pathway, thereby mitigating oxidative stress and ferroptosis.
研究领域:
药理学
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分子生物学
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肝病学
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细胞生物学
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生物化学
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PubMed
高影响因子
Chinese Medicine
·
2025
·Vol. 20
·期 1
·1-18
·
IF 5.7
Qiu Yuping,Li Shupei,Jiang Mingzuo,Huang Ang,Yang Ya,Chen Xi,Li Hui,Yang Zhizhou,Wei Juan,Xuan Ji
Background Lang Qing A Ta (Huagan Tongluo Fang, HGTLF) is a Tibetan medicine with significant anti-liver fibrosis effects and good efficacy in the treatment of liver diseases, including non-alcoholic fatty liver disease (NAFLD). Quercetagetin (QG) has been identified as an active ingredient of HGTLF that is absorbed into the blood. This study aims to investigate the role of QG in the anti-liver fibrosis effect of HGTLF in NAFLD. Methods CCl 4 injection-induced liver fibrosis and high-fat, high-cholesterol diet-induced non-alcoholic steatohepatitis (NASH) mouse models were established. Transforming growth factor-β1 (TGF-β1)-induced hepatic stellate cells (HSCs) were used as in vitro models. The effect of QG on the stability and degradation pathway of glu-tathione peroxidase 4 (GPX4) protein was investigated. Results QG improved liver function and hyperlipidemia in CCl 4 -injected mice and NASH mice, and alleviated hepatic lipid deposition and hepatic fibrosis. TGF-β1 treatment promoted the expression of α-smooth muscle actin and fibrosis-related genes, while QG reversed this phenomenon and inhibited HSC activation. QG increased the intracellular labile iron pool and lipid reactive oxygen species in HSCs. Treatment with the ferroptosis inhibitor ferrostatin-1 reversed the inhibitory effect of QG on TGF-β1-induced HSC activation. QG reduced GPX4 protein stability and regulated GPX4 K167 ubiquitination via the membrane-associated ring-CH-type finger 8 (MARCHF8)-mediated ubiquitin–proteasome pathway. Interference with MARCHF8 attenuated the effect of QG and promoted HSC activation induced by TGF-β1. Conclusion QG, the active ingredient of HGTLF, can induce ferroptosis of HSCs by targeting the degradation of GPX4 through ubiquitination and inhibit HSC activation, thereby alleviating liver fibrosis in NAFLD.
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PubMed
高影响因子
Advanced Healthcare Materials
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2025
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IF 9.6
Chen-Song Huang,Chunlei Dai,Qi Liu,Si-Yun Chen,Ya-Hao Guo,Jie-Qin Wang,An-Da Zheng,Xi-Tai Huang,Jun Wu,Xiao-Yu Yin
Ferroptosis has emerged as a critical mechanism in overcoming drug resistance in various tumors; however, its role in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) has not been thoroughly explored. Additionally, the effectiveness of ferroptosis in many cancer therapies has been limited. In our study, we found that GPX4 is upregulated in gemcitabine-resistant (GR) PDAC patient tissues and cell lines. Notably, inhibiting GPX4 can reverse gemcitabine resistance in PDAC through the induction of ferroptosis, highlighting it as a potential therapeutic target. To address this, we developed a novel nanomedicine, GSH-depleted and ferroptosis-induced (FiN), designed to encapsulate and deliver the GPX4 inhibitor RSL3, resulting in a dual ferroptosis-induced nanomedicine (DFiN). In a PDAC patient-derived xenograft (PDX) mouse model exhibiting gemcitabine resistance, DFiN demonstrated significant accumulation in GR PDAC tumors, leading to a reduction in intracellular GSH levels and inhibition of GPX4. This dual action promoted lipid peroxidation and synergistically induced ferroptosis, effectively reversing gemcitabine resistance. Both in vitro and in vivo experiments confirmed that DFiN is effective in overcoming gemcitabine resistance in GR PDAC cells and PDX tumors, with minimal toxicity observed. This study presents a promising strategy for addressing drug resistance in cancer therapy.
研究领域:
肿瘤学
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纳米医学
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分子生物学
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癌症治疗
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药理学
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PubMed
高影响因子
Scientific Reports
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2022
·Vol. 12
·期 1
·1-11
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IF 4.996
Wan Yiting,Gu Cancan,Kong Jueying,Sui Jin,Zuo Ling,Song Yanhua,Chen Jing
Endometriosis (EMs) is one of the most frequent diseases of reproductive-age women and is characterized by the growth of endometrial tissues beyond the uterus. The enhanced proliferative and migratory potential of endometrial stromal cells (ESCs) plays an important role in the progression of EMs. Mounting studies have demonstrated that long noncoding RNAs (lncRNAs) exert an important role in regulating the development and progression of EMs. Given the aberrant expression of lncRNA ADAMTS9-AS1 in ectopic endometrium (ecEM), we investigated the biological effect of ADAMTS9-AS1 on ESC proliferation and migration and explored the underlying mechanism. The current data showed that ADAMTS9-AS1 expression was significantly upregulated in ecEM compared with eutopic endometrium (euEM) in patients with EMs and in a murine model of EMs. Functionally, ADAMTS9-AS1 knockdown in ectopic ESCs (EESCs) decreased cell viability and migration, whereas ADAMTS9-AS1 overexpression in normal ESCs (NESCs) enhanced cell viability and migration. More importantly, the effect of ADAMTS9-AS1 inhibition on decreasing ESC viability was significantly blocked by ferrostatin-1 (Fer-1, a ferroptosis inhibitor), and ADAMTS9-AS1 overexpression repressed erastin (a ferroptosis activator)-induced cell death. Furthermore, the regulatory role of ADAMTS9-AS1 in ferroptosis was defined and evidenced by increased reactive oxygen species (ROS) levels and malonyl dialdehyde (MDA) content and decreased expression of glutathione peroxidase 4 (GPX4) after ADAMTS9-AS1 inhibition. Mechanistically, ADAMTS9-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-6516-5p to derepress the expression of GPX4, the critical repressor of ferroptosis. Taken together, these results demonstrate that upregulated ADAMTS9-AS1 accelerates ESC proliferation and migration by regulating miR-6516-5p/GPX4-dependent ferroptosis and may be a potential target for the treatment of EMs.
研究领域:
妇科学
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分子生物学
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细胞生物学
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PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2026
·Vol. 32
·期 4
·1-10
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IF 2.2
Wen Ouyang,Jianxin Gao,Jing Liu,Lulu Qin,Bang Liu,Ying He,Dai Zhou
Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.
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高影响因子
Food Production Processing and Nutrition
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2026
·Vol. 8
·期 1
·72
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IF 6.3
Niu Ruge,Xu Zhongchi,Yang Wenli,Bao Tong,Xu Fengsheng,Zhou Wenqi,Zhang Long,Jia Qi,Wang Xiaolong,Chen Jiandong,Lin Xin
Radiotherapy is a standard treatment for thoracic malignancies, but it frequently leads to radiation‑induced heart disease (RIHD), a serious and dose‑limiting complication for which no targeted therapies are currently available. Total extracts from Abelmoschus manihot (L.) (TEA), known for their cardioprotective properties, are widely used in treating various ischemic heart diseases. Here, we identify ferroptosis driven by the NOX4/SLC7A11/GPX4 axis as a core mechanism of RIHD, with GPX4 serving as the non‑redundant downstream executor. TEA effectively modulates this axis; however, it lacks cardiac selectivity, which may compromise antitumor efficacy. To overcome this barrier, we developed, characterized, and evaluated a novel nanoplatform consisting of TEA‑loaded PLGA nanoparticles conjugated with a primary cardiomyocyte‑specific homing peptide (PCM), further integrated with low-intensity focused ultrasound (LIFU)‑triggered on‑demand release (TEA@PLGA‑PCM). This system achieves superior myocardial accumulation, effectively improves cardiac function, reverses pathological remodeling, and normalizes ferroptosis markers as well as NOX4/SLC7A11/GPX4 protein expression. In summary, we successfully constructed a novel nanoplatform that represents a promising strategy for integrated targeted delivery and synergistic therapy in RIHD management. Graphical
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高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2025
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IF 3.4
Ruijing Li,Weili Yang,Lijuan Zheng,Xingxue Yan,Cuihua Liu,Yaodong Zhang,Jitong Li
Prenatal alcohol exposure is a leading cause of developmental abnormalities and neurobehavioral deficits, collectively known as fetal alcohol spectrum disorder (FASD). The underlying molecular mechanisms, however, are not fully elucidated, hindering the development of effective therapeutic strategies. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a key pathological process in various diseases. Gastrodin (GAS), the primary bioactive component of Gastrodia elata , has demonstrated potent antioxidant and neuroprotective properties. This study aimed to investigate the protective effects of GAS against alcohol-induced developmental and neurotoxic damage and to elucidate the underlying molecular mechanisms. Using a zebrafish larval model, we found that exposure to 200 mM alcohol from 2 to 24 hours post-fertilization (hpf) induced significant developmental toxicity, including a decreased hatching rate, body length and eye diameter, and increased morphological malformations in larvae. Alcohol-exposed larvae also exhibited severe neurobehavioral deficits, characterized by a reduction in movement distance and average velocity in dark conditions. Mechanistically, alcohol exposure triggered ferroptosis, evidenced by an increase in intracellular Fe 2+ , malondialdehyde (MDA), and reactive oxygen species (ROS) levels, alongside a decrease in the levels of glutathione (GSH) and reduced glutathione peroxidase 4 (GPX4) and the nuclear factor erythroid 2-related factor 2 (Nrf2) activities. Co-treatment with GAS (200 mg/L) significantly ameliorated these alcohol-induced developmental and neurobehavioral defects. GAS administration effectively suppressed the hallmarks of ferroptosis by restoring the ROS level and altering the expression of genes related to oxidative stress. In addition, GAS suppressed alcohol-induced cell apoptosis, downregulated caspase3b , bax , caspase8 , and upregulated bcl2 in mRNA levels. Molecular analysis revealed that GAS exerts its anti-ferroptotic effect by activating Nrf2/GPX4 signaling pathway, which was suppressed by alcohol. Our findings indicate that ferroptosis plays a key role in alcohol-induced developmental neurotoxicity, and GAS provides protection by activating the Nrf2/GPX4 axis. This suggests that GAS could be a potential therapeutic option for reducing the negative effects of prenatal alcohol exposure.
研究领域:
神经毒理学
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发育生物学
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分子药理学
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氧化应激研究
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斑马鱼模型
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PubMed
高影响因子
TISSUE & CELL
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2025
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IF 2.5
Jie Liu,Yuan-Yuan Xu,Tian-Ye Gao
Background Diabetic kidney disease (DKD) is a severe microvascular complication, and ferroptosis is a major contributor to its pathogenesis. This study investigated the protective effects of Qingyu formula (QYF), a traditional Chinese medicine prescription, against ferroptosis in high glucose-induced renal injury. Methods In vitro, human renal tubular cells (human kidney 2 [HK-2]) under high glucose conditions were treated with QYF. In vivo, the induced diabetic mice received QYF interventions. Biochemical and molecular assays assessed cell viability, oxidative stress, ferroptosis markers (Fe²⁺, glutathione [GSH], malondialdehyde) and nuclear factor erythroid 2-related factor 2/solute carrier family 7 member 11/glutathione peroxidase 4 (Nrf2/SLC7A11/GPX4) pathway activity. Results Qingyu formula enhanced cell viability and reduced reactive oxygen species in high glucose-treated HK-2 cells. It mitigated ferroptosis by decreasing Fe²⁺ accumulation and increasing GSH levels both in vivo and in vitro. Mechanistically, QYF upregulated GPX4, Nrf2 and SLC7A11. In diabetic mice, it improved metabolic parameters and reduced proteinuria in a dose-dependent manner, with high doses showing efficacy similar to that of clinically used irbesartan. Conclusions Qingyu formula protects against high glucose-induced renal injury by suppressing ferroptosis via the activation of the Nrf2/SLC7A11/GPX4 pathway. These findings support QYF as a promising candidate for targeting ferroptosis in DKD. Future studies should identify its active constituents and evaluate its efficacy in clinical trials.
研究领域:
药理学
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肾脏病学
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分子生物学
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中医中药
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细胞生物学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Xun Sun,Xinyu Zhang,Hui Yan,Hongfei Wu,Shijian Cao,Wenchen Zhao,Ting Dong,An Zhou
Background Hepatolenticular degeneration (HLD) is an autosomal recessive disorder concerning copper metabolism . Copper overload is also accompanied by iron overload in HLD patients , which can lead to ferroptosis . Curcumin , the active component in turmeric, has the potential to inhibit ferroptosis. Purpose The current study proposed a systematic investigation of the protective effects of curcumin against HLD and the underlying mechanisms. Methods The protective effect of curcumin on toxic milk (TX) mice was studied. Liver tissue was observed via hematoxylin-eosin (H&E) staining and the ultrastructure of the liver tissue was observed through transmission electron microscopy . Copper levels in the tissues, serum, and metabolites were measured by atomic absorption spectrometry (AAS). In addition, serum and liver indicators were evaluated. In cellular experiments, the effect of curcumin on the viability of rat normal liver cells (BRL-3A) was determined via the 3-[4,5-dimethylthiazol-2-yl)]-2,5-diphenyltetrazolium bromide (MTT) assay. Cell and mitochondrial morphology were observed in curcumin-mediated HLD model cells. The intracellular copper ion fluorescence intensity was observed via fluorescence microscopy , and intracellular copper iron content was detected using AAS. Further, oxidative stress indicators were evaluated. Cellular reactive oxygen species (ROS) and cellular mitochondrial membrane potential were examined via flow cytometry. Furthermore, the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutathione peroxidase 4 (GPX4) were determined via western blotting (WB). Results The histopathology of the liver confirmed the hepatoprotective effects of curcumin. Curcumin improved copper metabolism in TX mice. Both serum liver enzyme markers and antioxidant enzyme levels indicated the protective effect of curcumin against HLD-related liver injury. The MTT assay results showed that curcumin was protective against excess copper-induced injury. Curcumin improved the morphology of HLD model cells and their mitochondrial morphology. The Cu 2+ fluorescent probe and the AAS results indicated that curcumin reduced Cu 2+ content in HLD hepatocytes. In addition, curcumin improved oxidative stress levels and prevented the decline of mitochondrial membrane potential in HLD model cells. The ferroptosis inducer Erastin reversed these effects of curcumin. WB revealed that curcumin promoted Nrf2, HO-1, and GPX4 protein expression in HLD model cells, and the Nrf2 inhibitor ML385 reversed the effects of curcumin. Conclusion Curcumin demonstrates a protective role by expelling copper and inhibiting ferroptosis, activating the Nrf2/HO-1/GPX4 signaling pathway in HLD.
研究领域:
药理学
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毒理学
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分子生物学
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细胞生物学
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神经病学
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PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
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IF 9.273
Ziting Zhang,You Ji,Nan Hu,Qinqi Yu,Xinrui Zhang,Jie Li,Fenglei Wu,Huae Xu,Qiyun Tang,Xiaolin Li
Ferroptosis is a novel form of programmed cell death impelled by iron-dependent lipid peroxidation, which may be a potential strategy for cancer therapy. Here we demonstrated for the first time that Resveratrol (RSV), a traditional Chinese medicine (TCM) chemical monomer, could effectually inhibit the growth of colon cancer cells through the ROS-dependent ferroptosis pathway. Mechanistically, RSV evoked the increase of reactive oxygen species and lipid peroxidation in colorectal cancer cells, and eventually lead to ferroptosis. Furthermore, RSV could promote ferroptosis by downregulating the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). To improve the delivery efficiency of RSV, a biomimetic nanocarrier was developed by coating RSV-loaded poly(ε-caprolactone)–poly(ethylene glycol) (PCL-PEG) nanoparticles with erythrocyte membrane ( [email protected] ). The [email protected] provide the possibility to escape macrophage phagocytosis and have a long circulation effect. In addition, when coupled with a tumor-penetrating peptide iRGD, which could trigger enhanced tissue penetration tumor-specifically, the delivery of [email protected] into tumors would be significantly improved results from the in vivo study demonstrated an excellent treatment efficacy for CRC. Altogether, our study highlighted the therapeutic potential of RSV as a ferroptosis-inducing anticancer agent and when loaded into a biomimetic nanoplatform, it might pave the way for the application of RSV loaded nanosystems for colorectal cancer treatment.
研究领域:
肿瘤学
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药理学
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纳米技术
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生物医学工程
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DOI
PubMed
高影响因子
Frontiers in Oncology
·
2021
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IF 6.244
Yuan Yin,Ni Shuo,Zhuge Aoxiang,Li Bo,Li Lanjuan
Iron promotes the proliferation of cancer cells, but it also contributes to cell death. Here we explored whether iron could promote the Warburg effect of colorectal cancer (CRC) cells and suppress sensitivity to ferroptosis by inducing reactive oxygen species (ROS) and regulating nuclear factor erythroid 2-related factor 2 (NRF2). In this study, cell proliferation abilities were measured by CCK-8, EdU incorporation, and colony formation assays. Seahorse XF96 respirometry assays were used to detect the Warburg effect and the level of ROS was assess by DCFH-DA fluorescent probes. Results showed that iron exposure promoted the Warburg effect of CRC cells by inducing ROS and activating NRF2 both in vivo and in vitro. In addition, iron exposure also induced ferroptosis in CRC cells, but at the same time its inhibitory proteins SLC7A11 and GPX4 were also upregulated, indicating an enhanced resistance to ferroptosis. Our results revealed that iron can effectively promote tumorigenesis. Meanwhile, iron elimination or a low-iron diet might be valid therapeutic approaches for CRC.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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PubMed
高影响因子
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