JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2026
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IF 9.7
Fei Xu,Yingqi Gao,Xiaoxiao Zhou,Jing Cui,Ruozheng Wei,Tao Peng
The treatment of pancreatic cancer has long been a global challenge. Strategies based on mitochondrial Ca 2+ overload-related ferroptosis have garnered significant attention. However, the various limitations of current Ca 2+ generators make it difficult to maintain an effective concentration of Ca 2+ overload. In this study, we developed a nanocomposite material, CaO 2 @Fe( SS )-MOF@Ce6@PAA (CFMCP), by encapsulating CaO 2 nanoparticles (NPs) and the photosensitizer Chlorin e6 (Ce6) within a metal-organic framework (MOF) and further modifying it with polyacrylic acid (PAA). This nanocomposite effectively depletes glutathione (GSH) in tumor tissues, thereby enhancing the efficacy of photodynamic therapy (PDT) and chemodynamic therapy (CDT). Upon co-incubation of CFMCP NPs with SW1990 pancreatic cancer cells, we observed efficient cellular uptake of the nanomaterials. Under the influence of CFMCP NPs, cellular GSH and glutathione peroxidase 4 (GPX4) levels decreased, exacerbating oxidative stress and lipid peroxidation, increasing Fe 2+ content, and aggravating mitochondrial damage. Using the mitochondrial Ca 2+ uptake inhibitor Ruthenium red, we further confirmed that Ca 2+ overload is a critical mechanism by which CFMCP NPs induce ferroptosis in SW1990 cells. In vivo studies demonstrated that CFMCP NPs exhibit excellent biocompatibility, significantly inhibit tumor growth, and exert direct cytotoxic effects. In summary, the development of this novel composite nanomaterial, which induces ferroptosis through mitochondrial Ca 2+ overload, provides a valuable reference for synergistic and highly effective tumor therapy.
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高影响因子
PHYTOTHERAPY RESEARCH
·
2024
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IF 6.1
Jianxia Wen,Lu Li,Yi Yang,Dinglin Ou,Junjie Yang,Jiachen Xie,Wenya Du,Yuling Tong
Ferroptosis is a form of iron-dependent regulatory cell death that is related to the pathogenesis and progression of various cardiovascular diseases, such as arrhythmia, diabetic cardiomyopathy, myocardial infarction, myocardial ischemia/reperfusion injury, and heart failure. This makes it a promising therapeutic target for cardiovascular diseases. It is interesting that a significant number of cardiovascular disease treatment drugs derived from phytochemicals have been shown to target ferroptosis, thus producing cardioprotective effects. This study offers a concise overview of the initiation and control mechanisms of ferroptosis. It discusses the core regulatory factors of ferroptosis as potential new therapeutic targets for various cardiovascular diseases, elucidating how ferroptosis influences the progression of cardiovascular diseases. In addition, this review systematically summarizes the regulatory effects of phytochemicals on ferroptosis, emphasizing their potential mechanisms and clinical applications in treating cardiovascular diseases. This study provides a reference for further elucidating the molecular mechanisms of phytochemicals in treating cardiovascular diseases. This may accelerate their application in the treatment of cardiovascular diseases and is worth further research in this field.
研究领域:
药理学
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心脏病学
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分子生物学
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高影响因子
ACS Applied Nano Materials
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2026
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IF 5.8
Yibo Song,Yixin Li,Shihao Zheng,Shu-Feng Zhou,Guowu Zhan
Copper-based nanomaterials hold immense potential for cancer therapy by inducing chemodynamic therapy and cuproptosis. However, their therapeutic efficacy is severely restricted by insufficient tumor accumulation, the potent antioxidant effects of elevated intracellular glutathione (GSH), and tumor adaptability to single-mechanism treatments. To address these challenges, we designed a pH/GSH dual-responsive nanosystem (CuSiO3@POM) by integrating molybdenum-based polyoxometalate (POM) clusters with a copper phyllosilicate platform. In the acidic tumor microenvironment (TME), POM drives in situ self-assembly into large aggregates, significantly enhancing tumor retention and local copper concentration. Upon cellular internalization, the elevated copper accumulation triggers cuproptosis; meanwhile, the overexpressed endogenous GSH reduces Cu2+ and Mo6+ to Cu+ and Mo5+, resulting in profound GSH depletion. Following this reduction, Cu+ catalyzes Fenton-like reactions to yield hydroxyl radicals (·OH), while Mo5+ generates singlet oxygen (1O2) via the Russell mechanism. This synergistic burst of reactive oxygen species triggers severe lipid peroxidation and subsequent ferroptosis. Furthermore, the reduced Mo5+ serves as an efficient agent for photothermal therapy (PTT) under NIR irradiation, which thermally amplifies the oxidative damage. By orchestrating cuproptosis, ferroptosis, and photothermal enhancement within a single TME-responsive platform, CuSiO3@POM provides a highly efficient multimodal strategy to overcome the limitations of conventional copper-based therapies.
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TISSUE & CELL
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2026
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IF 3.1
Dayuan Zheng,Dongfan Yang,Tong Chu,Shaokui Liang,Kuanyun Zhang,Lu Yang,Yanchao Yang,Wenzhe Ma
YB overcomes chemoresistance in EBV-positive NPC. • YB induces ferroptosis rather than necroptosis in EBV-positive NPC. • YB activates ferritinophagy-dependent ferroptosis in EBV-positive NPC. • NCOA4 knockdown rescues YB-treated EBV-positive NPC. Background EBV-positive nasopharyngeal carcinoma frequently exhibits significant chemoresistance, posing a major challenge in clinical treatment. Yunnan Baiyao, a traditional Chinese patent medicine, has shown promise in antitumor research beyond its conventional hemostatic applications. This study investigated the efficacy of Yunnan Baiyao against EBV-positive nasopharyngeal carcinoma and explored the underlying molecular mechanisms of cell death. Methods Yunnan Baiyao-treated EBV-positive C666–1 and EBV-negative HK1/SUNE1 cells were subjected to Sulforhodamine B assay, colony formation assay, and C11-BODIPY/Fe²⁺ flow cytometry to verify antitumor activity and ferroptosis induction. Ferroptosis, autophagy, and ferritinophagy were confirmed via live-cell imaging, Transmission Electron Microscopy, and Western blotting. Specific inhibitors (Q-VD-Oph, Nec-1, etc.) validated the roles of apoptosis, necroptosis, and other pathways. Lentiviral NCOA4 knockdown verified its core function. Nude mouse xenograft models (with Liproxstatin-1 rescue and NCOA4-knockdown tumors) evaluated in vivo efficacy and dependence on ferroptosis/NCOA4. Results C666–1 cells (EBV-positive) are more resistant to cisplatin compared with SUNE1 and HK1 cells (both EBV-negative). Yunnan Baiyao exerted concentration- and time-dependent cytotoxicity on C666–1 cells. Notably, C666–1 cells were more sensitive to Yunnan Baiyao than SUNE1 cells. Yunnan Baiyao induced ferroptosis (not apoptosis/necroptosis/pyroptosis) with elevated lipid peroxidation, intracellular Fe²⁺ accumulation, and mitochondrial shrinkage. Yunnan Baiyao activated autophagic flux, and BAF (autophagy inhibitor) partially reversed ferroptosis. Yunnan Baiyao-induced cell death relied on NCOA4-mediated ferritinophagy; NCOA4 knockdown abrogated its effects in vitro. In vivo, Yunnan Baiyao significantly inhibited tumor growth, reversed by Lip-1 treatment or NCOA4 knockdown. Conclusions Yunnan Baiyao overcomes chemoresistance in EBV-positive nasopharyngeal carcinoma by triggering NCOA4-mediated ferritinophagy-dependent ferroptosis. These findings provide a mechanistic foundation for further preclinical evaluation of Yunnan Baiyao as a candidate therapeutic strategy for chemoresistant nasopharyngeal carcinoma. Download: Download high-res image (146KB) Download: Download full-size image
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Frontiers in Pharmacology
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2026
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IF 5.4
Liang Zhang,Huan Liu,Si Jiang,Desheng Li,Xin Li,Maolei Xu,Jianwen Fei,Ling Zhou
Background The natural compound morusin (Mor) acts as a potent tumor suppressor in non-small cell lung cancer (NSCLC), but its potential to sensitize DDP and its direct targets are less understood. This work aims to investigate the DDP-sensitizing effects of Mor and the underlying mechanisms. Methods Cell viability and drug synergy were assessed in NSCLC cells. Ferroptosis was evaluated by measuring lipid reactive oxygen species (ROS), iron accumulation, and the expression of ferroptosis markers. GDF15 was identified as a target via transcriptome sequencing. Its direct binding with Mor was confirmed by molecular docking. The ubiquitin-mediated degradation mechanism and its functional role in ferroptosis were validated using the proteasome inhibitor MG132, alongside GDF15 overexpression and knockdown models. Clinical relevance was assessed using TCGA database analysis. Results Mor induces ferroptosis and significantly augments DDP sensitivity in both NSCLC and cisplatin-resistant A549 cells (A549/DDP). Mechanistically, Mor directly binds to GDF15 and promotes its ubiquitin-mediated degradation. Consequently, GDF15 overexpression reversed Mor-induced cytotoxicity and DDP sensitization. Furthermore, DDP exposure impairs intracellular GDF15 protein levels, and the Mor/DDP combination synergistically suppresses GDF15 in A549 cells. Notably, GDF15 expression is elevated in NSCLC cells compared to normal lung epithelial cells. However, A549/DDP cells exhibit diminished intracellular GDF15 protein relative to parental cells, while GDF15 transcription is upregulated. Knockdown of GDF15 augmented DDP sensitivity in resistant cells. Conclusion Mor reverses DDP resistance by inducing GDF15 degradation and ferroptosis, suggesting that Mor-based combination therapy holds promise in treating NSCLC.
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高影响因子
Alzheimers Research & Therapy
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2026
·Vol. 18
·期 1
·66
·
IF 8.9
Lv Lifang,Jia Yuhan,Zhang Chi,Gao Qiang,Han Huiming,Li Jiaxin,Cai Zhenhua,Liu Meiqi,Zhang Ying,Liu Jinfeng,Zhu Hui
Background Ferroptosis has been implicated in the pathogenesis of Alzheimer’s disease (AD), yet its upstream neuronal regulators remain unclear. This study investigated the mechanisms by which melatonin exerts neuroprotection, focusing on the glutamine transporter solute carrier family 38 member 2 (SLC38A2), which inhibits ferroptosis in AD. Methods AD models included C57BL/6 mice injected intracerebroventricularly with beta-amyloid (Aβ) 1-42 oligomers, organotypic hippocampal slices treated with Aβ 1-42 oligomers, and HT22 hippocampal neurons treated with hydrogen peroxide. Cognition and hippocampal pathology were assessed by open field test, Morris water maze (MWM), shuttle box tests, and histology. Cross-species multi-omics comprised single-cell RNA sequencing of human hippocampus, mouse spatial transcriptomics, human bulk RNA sequencing and proteomics. Protein changes were measured by immunohistochemistry, immunofluorescence and Western blotting. Biochemical assays quantified glutathione (GSH), malondialdehyde (MDA), iron, and reactive oxygen species (ROS). Results In Aβ 1-42 oligomer-injected C57BL/6 mice, melatonin improved cognition in MWM and shuttle box tests without affecting locomotion, reduced hippocampal neuronal loss, and lowered Aβ/Tau/p-Tau. Single-cell RNA sequencing of human hippocampus and spatial transcriptomics in the mouse brain demonstrated pronounced ferroptosis in the AD hippocampal region. Integrative human proteomics, bulk RNA sequencing and spatial transcriptomics prioritized the downregulation of the glutamine-family amino-acid catabolic process and identified SLC38A2 as a key node. In vivo and in organotypic hippocampal slices, melatonin reversed the Aβ 1-42 oligomer-induced ferroptosis signature. Immunohistochemistry, immunofluorescence, and Western blotting showed that melatonin upregulated SLC38A2 in the Aβ-treated hippocampus and slices. Functionally, shRNA-mediated SLC38A2 knockdown in HT22 neurons reduced GSH and glutathione peroxidase 4 (GPX4), increased iron and ROS, enhanced erastin-induced ferroptosis, and abolished the protective effect of melatonin. Conclusions These findings identify SLC38A2 as a pivotal regulator of hippocampal ferroptosis and demonstrate that melatonin confers neuroprotection by stabilizing the SLC38A2-GSH-GPX4 axis, supporting SLC38A2 as a therapeutic target in AD.
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高影响因子
BMEMat
·
2026
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IF 17.2
Panpan Xue,Hai Cai,Ying Sun,Yaxin Ma,Siyuan Liu,Jinying Zhu,Yan Chen,Xuemei Zeng,Shuangqian Yan
Metastatic cancer remains difficult to treat due to the immunosuppressive tumor microenvironment and the absence of effective strategies to elicit durable systemic immunity. Ferroptosis, an iron-dependent form of immunogenic cell death, holds promise but most inducers exhibit limited efficacy and poor engagement with innate immune sensing. Here, we present a bioinspired nanoplatform (MnMSN@MnP-PEG) that co-delivers manganese peroxidase (MnP) and Mn 2+ /Mn 3+ ions to synergistically trigger ferroptosis and activate the cGAS–STING pathway. Manganese peroxidase, inspired by its natural role in lignin degradation, directly catalyzes lipid peroxidation using tumor-associated H 2 O 2 . The Mn 2+ -doped silica carrier not only ensures MnP delivery but also exhibits glutathione oxidase- and peroxidase-like activities, amplifying oxidative stress and disrupting redox homeostasis. This cascade induces extensive lipid peroxidation and immunogenic ferroptosis, provoking robust innate and adaptive immune responses, including dendritic cell maturation, T cell and natural killer cell infiltration, and macrophage repolarization. Remarkably, a single intravenous injection eradicates primary tumors, suppresses distant tumor growth, and prevents pulmonary metastasis in murine models. Our study establishes a “catalytic immunotherapy” paradigm that leverages fungal enzymatic activity for systemic cancer treatment.
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Small Methods
·
2025
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IF 9.1
Zheng Chen,Qiyue Wang,Sirui Cui,Xi Hu,Peihua Lin,Bo Zhang,Daishun Ling,Fangyuan Li
Piezoelectric materials have emerged as versatile tools for ultrasound-triggered cancer therapy, yet their clinical application is constrained by inefficient charge separation and the limited availability of catalytic substrates in the tumor microenvironment. Here, an electronegativity-modulated piezoelectric metal–organic framework (CapMOF@HA) is reported through controlled heteroepitaxial growth of CaO 2 on pMOFs, followed by surface functionalization with hyaluronic acid (HA) for tumor-targeting capability for enhanced piezocatalytic therapy. Of note, the electronegativity-modulated heterogeneous interfaces between CaO 2 and pMOF promote the separation of electron–hole pairs while suppressing recombination through the electronegativity effect, significantly amplifying piezocatalytic reactive oxygen species (ROS) generation (•OH, 1 O 2 , and •O 2 ⁻) under ultrasound stimulation. Furthermore, the controlled decomposition of calcium peroxide provides a continuous supply of H 2 O 2 and O 2 as catalytic substrates, while releasing Ca 2+ to induce calcium overload, triggering mitochondrial dysfunction and glutathione peroxidase 4 inhibition for ferroptosis induction. This strategy integrates enhanced piezoelectric catalysis with ferroptosis induction, overcoming long-standing limitations in piezocatalytic systems to achieve precise and robust tumor ablation. By combining substrate self-sufficiency with multifunctional therapeutic mechanisms, this work establishes tumor piezocatalytic ferroptosis as a transformative platform for next-generation piezoelectric cancer therapy.
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Cell Death Discovery
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2025
·Vol. 11
·期 1
·1-17
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IF 7
Wei Guojiang,Huang Ying,Li Wenya,Xie Yuxin,Zhang Deyi,Niu Yuanjie,Zhao Yang
Metabolic reprogramming in prostate cancer has been widely recognized as a promoter of tumor progression and treatment resistance. This study investigated its association with ferroptosis resistance in prostate cancer and explored its therapeutic potential. In this study, we identified differences in the epithelial characteristics between normal prostate tissue and tissues of various types of prostate cancer using single-cell sequencing. Through transcription factor regulatory network analysis, we focused on the candidate transcription factor, SREBF1. We identified the differences in SREBF1 transcriptional activity and its association with ferroptosis, and further verified this association using hdWGCNA. We constructed a risk score based on SREBF1 target genes associated with the biochemical recurrence of prostate cancer by combining bulk RNA analysis. Finally, we verified the effects of the SREBPs inhibitor Betulin on the treatment of prostate cancer and its chemosensitization effect. We observed characteristic differences in fatty acid and cholesterol metabolism between normal prostate tissue and prostate cancer tissue, identifying high transcriptional activity of SREBF1 in prostate cancer tissue. This indicates that SREBF1 is crucial for the metabolic reprogramming of prostate cancer, and that its mediated metabolic changes promoted ferroptosis resistance in prostate cancer in multiple ways. SREBF1 target genes are associated with biochemical recurrence of prostate cancer. Finally, our experiments verified that SREBF1 inhibitors can significantly promote an increase in ROS, the decrease in GSH, and the decrease in mitochondrial membrane potential in prostate cancer cells and confirmed their chemosensitization effect in vivo. Our findings highlighted a close association between SREBF1 and ferroptosis resistance in prostate cancer. SREBF1 significantly influences metabolic reprogramming in prostate cancer cells, leading to ferroptosis resistance. Importantly, our results demonstrated that SREBF1 inhibitors can significantly enhance the therapeutic effect and chemosensitization of prostate cancer, suggesting a promising therapeutic potential for the treatment of prostate cancer.
研究领域:
肿瘤学
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分子生物学
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生物信息学
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JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Congcong Lin,Jiamin Sun,Yun Yang,Xinyao Pan,Shiyu Wang,Xiaoyang Li,Yan Zhang,Huile Gao,Chunli Gan
The development of chemotherapy resistance poses a major challenge in cancer therapy. Ferroptosis, a unique type of cell death, offers a promising strategy to combat this resistance. Herein, a peptide-based nanoassembly (PTX@CPG) consisting of paclitaxel (PTX), chlorin e6 (Ce6), and FFVLKPLGLAGK-(PEG8) 3 was constructed to promote ferroptosis through reactive oxygen species (ROS) accumulation and overcome chemoresistance. Specifically, the small-sized PTX@CPG nanoparticles effectively penetrate tumors, where the microenvironment-responsive peptide is selectively cleaved by the high expression of matrix metalloproteinase 2. This process facilitates the targeted release of PTX and its reassembly into nanofibers, improving the tumor retention of Ce6 and enhancing its cellular uptake. The synergistic therapeutic effects of PTX in combination with photodynamic therapy on triple-negative breast cancer cells were validated through both in vitro and in vivo experiments. Impressively, upon laser irradiation, PTX@CPG significantly increased ROS production, thereby amplifying the ferroptosis-inducing effects of PTX. Moreover, ferroptosis triggered by PTX@CPG with laser reduced the levels of P-glycoprotein and glutathione peroxidase 4, contributing to the alleviation of chemoresistance. Overall, PTX@CPG with laser demonstrated effective spatial targeting and drug retention, enhancing ferroptosis through ROS accumulation and showcasing a promising approach for overcoming chemotherapy resistance in cancer therapy.
研究领域:
肿瘤学
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纳米医学
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药理学
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Food Science & Nutrition
·
2025
·Vol. 13
·期 5
·e70254
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IF 3.8
Yujie Pan,Mingyan Xia,Jin Luo,Shuai Lu
Diabetic wound healing critically depends on functional endothelial cells for angiogenesis, yet the hyperglycemic microenvironment induces endothelial dysfunction through oxidative stress, inflammation, and senescence. Although ferroptosis has been recognized as a critical pathological factor contributing to impaired diabetic wound healing, the therapeutic potential of resveratrol (Res), a natural polyphenol with well‐documented antioxidant and anti‐ferroptotic properties, remains underexplored in this context. This study aimed to investigate the protective effects of Res on endothelial cells and elucidate its underlying mechanisms in diabetic wound healing. In vitro experiments systematically evaluated Res's impact on cellular inflammatory responses, senescence levels, and angiogenic capacity. Subsequent in vivo studies assessed Res's therapeutic potential by monitoring diabetic wound healing progression and analyzing associated histological changes. To clarify the mechanisms underlying Res's promotion of diabetic wound healing, we conducted comprehensive analyses measuring intracellular reactive oxygen species, lipid peroxidation levels, mitochondrial membrane potential and morphology, ferroptosis‐related marker expression, and upstream signaling pathway regulation. Res significantly reduced HG‐induced inflammatory responses and cellular senescence in human umbilical vein endothelial cells while enhancing their angiogenic potential in vitro. In vivo results showed that Res not only markedly accelerated diabetic wound healing but also demonstrated multiple beneficial effects, including effective suppression of cellular senescence, decreased ferroptosis levels, and significantly promoted angiogenesis. Mechanistic investigations confirmed that Res achieves these effects by inhibiting ferroptosis through activation of the PI3K‐AKT‐Nrf2 signaling axis. Our results demonstrate that Res protects endothelial cells from HG‐induced ferroptosis by activating PI3K‐AKT‐Nrf2 signaling, thereby promoting angiogenesis and diabetic wound healing. These findings highlight Res as a promising therapeutic candidate for impaired diabetic wound repair and justify further clinical investigation. Resveratrol attenuates intracellular inflammatory responses and cellular senescence by inhibiting ferroptosis via activating the PI3K‐AKT‐Nrf2 signaling pathway, ultimately facilitating angiogenesis and healing of diabetic wounds.
研究领域:
医学
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药理学
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分子生物学
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Advanced Composites and Hybrid Materials
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2025
·Vol. 8
·期 4
·1-18
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IF 21.8
Wang Pengfei,Sun Xinxin,Feng Chengcheng,Liu Shiwen,Chen Qin,Zhang Shenwu,Sun Jin,He Zhonggui,Wang Yuequan,Luo Cong
Ferroptosis has emerged as a promising anticancer target, while the clinical translation of ferroptosis inducers is greatly obstructed by the heterogeneous iron levels and inherent antioxidant defense in tumors. Given that most ferroptosis inducers alone fail to elicit cellular lipid peroxidation storm, we here design a ferroptosis booster to synergize with inducers to trigger cellular ROS eruption. Inspired by the pharmacological mechanisms of artesunate (ART), a functional ART-ferrocene (ART-Fc) conjugate is synthesized by esterification reaction. Encouragingly, ART-Fc remarkably sensitizes a variety of ferroptosis inducers through close-by iron supply and productive ROS generation, establishing it as a potential ferroptosis booster. To validate the concept, a binary nanohybrid of sorafenib (Sor) and ART-Fc is fabricated to cooperatively induce tumor ferroptosis. ART-Fc renders iron overload and raises ROS storm through close-by iron supply and intramolecular electron transfer from Fc to ART, which significantly boosts Sor-induced ferroptosis in heterotopic and orthotopic triple-negative breast cancer mouse models. This study presents a broad-spectrum synergist designed to enhance the efficacy of ferroptosis-based cancer therapies and advances an iron overload/ROS eruption/GSH depletion "triple punch" nanotherapeutics towards clinical treatment of triple-negative breast cancer.
研究领域:
纳米技术
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肿瘤学
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药理学
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生物化学
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材料科学
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