Microsystems & Nanoengineering
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2025
·Vol. 11
·期 1
·1-10
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IF 9.9
Ma Yanmei,Li Xinhao,Hu Weikang,Ruan Muyang,Yang Ming,Chang Lingqian,Gu Hongri,Hu Chengzhi
Ferroptosis is an iron-dependent form of regulated cell death driven by phospholipid peroxidation and the accumulation of reactive oxygen species (ROS), holding significant importance for therapeutic applications via its induction or inhibition. Accurate detection of intracellular Fe 2+ and ROS is essential, as these molecules play essential roles in initiating and propagating ferroptosis. In this study, we present a novel electrochemical nanoprobe for real-time, highly selective detection of intracellular Fe 2+ . The nanoprobes are prepared by coating gold nanoparticles (AuNPs) and poly(3,4-ethylenedioxythiophene) (PEDOT) onto silicon carbide nanowires (SiC NWs), which are subsequently functionalized with ferrocenyl endoperoxide carboxylic acid (FDCA) and integrated with a liquid metal-filled glass nanopipette. FDCA is specifically synthesized to enable precise electrochemical detection of Fe 2+ with high selectivity (0.1 nM to 1 µM) and exceptional specificity. PEDOT and AuNPs can improve electrical conductivity and provide a versatile interface for further FDCA decoration. We use the nanoprobes to evaluate the intracellular change of Fe 2+ in MCF-7 breast cancer cells during erastin-induced ferroptosis. We observe a significant increase in intracellular Fe 2+ levels in MCF-7 cells undergoing ferroptosis, accompanied by a notable rise in ROS levels. These findings underscore the potential of this nanoprobe to enhance our understanding of the mechanism of ferroptosis in tumor development and as a potential treatment target.
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REDOX REPORT
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2025
·
IF 7.4
Siqi Zhu,Jingyi Ren,Yadong Zhang,Xiaoya Sun,Huanting Pei,Bowen Yin,Ziyi Wang,Zhenao Zhang,Shenghe Li,Ruonan Zhang,Ziqian Zeng,Yuxia Ma
Background Acetaminophen (APAP) is a widely used antipyretic and analgesic agent, and acute exposure can lead to renal injury. Sesamin (Ses) is known for its various health benefits. However, it remains unclear whether Ses exerts a protective effect against APAP-induced kidney injury.Methods In vivo, C57BL/6 mice were pretreated with Ses and injected intraperitoneally with APAP. In vitro, human kidney proximal tubule cells 2 were pretreated with Ses, and then models of kidney injury induced by APAP were established. Kidney damage was evaluated by morphological, inflammation, oxidative stress and protein analyzes.Results Ses significantly improved APAP-induced nephrotoxicity in vitro and in vivo models. Transcriptomic analysis revealed that the differentially expressed genes were enriched in ferroptosis and apoptosis signaling pathways, identifying heme oxygenase 1 (HMOX1) as a core protein. In the Ses-treated group, ferroptosis and apoptosis were significantly inhibited, while HMOX1 was effectively restored. In cell experiments, both the HMOX1 agonist hemin and Ses attenuated ferroptosis and apoptosis. HMOX1 inhibitor Zinc Protoporphyrin significantly eliminated the protective effect of Ses.Conclusion Ses alleviates APAP-induced renal injury by mediating the inhibition of ferroptosis and apoptosis via HMOX1. This study provides a new strategy for the prevention and treatment of drug-induced renal injury.
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ACS Nano
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2024
·
IF 15.8
Lanlan Fan,Panyu Du,Yaru Li,Xuefei Chen,Fang Liu,Yuning Liu,Alexey M. Petrov,Xin Li,Zheng Wang,Yanjun Zhao
Ferroptotic cancer therapy has been extensively investigated since the genesis of the ferroptosis concept. However, the therapeutic efficacy of ferroptosis induction in heterogeneous and plastic melanoma has been compromised, because the melanocytic and transitory cell subpopulation is resistant to iron-dependent oxidative stress. Here, we report a phenotype-altering liposomal nanomedicine to enable the ferroptosis-resistant subtypes of melanoma cells vulnerable to lipid peroxidation via senescence induction. The strategy involves the ratiometric coencapsulation of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor (palbociclib) and a ferroptosis inducer (auranofin) within cRGD peptide-modified targeted liposomes. The two drugs showed a synergistic anticancer effect in the model B16F10 melanoma cells, as evidenced by the combination index analysis (<1). The liposomes could efficiently deliver both drugs into B16F10 cells in a targeted manner. Afterward, the liposomes potently induced the intracellular redox imbalance and lipid peroxidation. Palbociclib significantly provoked cell cycle arrest at the G0/G1 phase, which sensitized auranofin-caused ferroptosis through senescence induction. Meanwhile, palbociclib depleted intracellular glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH), further boosting ferroptosis. The proof-of-concept was also demonstrated in the B16F10 tumor-bearing mice model. The current work offers a promising ferroptosis-targeting strategy for effectively treating heterogeneous melanoma by manipulating the cellular plasticity.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
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IF 5.4
Xieyu Yan,Quanjin Li,Shuai Xiao,Junjie Chen,Wei Song
Promoting ferroptosis in tumor cells has emerged as a promising strategy for cancer therapy. Nonetheless, the heightened antioxidant activity within tumor cells hampers this approach, diminishing its effectiveness and fostering drug resistance. In this study, a new type of sulfasalazine (SAS) loaded nanoframe self-etched Pt-Co nanodendrites (Pt/Co-BNN@SAS) was developed, presenting a novel avenue for inducing ferroptosis in tumor cells by depleting glutathione (GSH) for cancer treatment. Pt/Co-BNN exhibits notable peroxidase (POD) activity, catalyzing the production of abundant oxygen radicals through the consumption of hydrogen peroxide (H 2 O 2 ) and the concurrent depletion of GSH. Simultaneously, the liberated sulfasalazine (SAS) from Pt/Co-BNN@SAS effectively obstructs system xc - , impeding the absorption of cystine by tumor cells and thereby expediting GSH depletion. The expeditious reduction of GSH markedly stimulates the accumulation of lipid peroxides (LPO) and suppresses glutathione peroxidase 4 (GPX4), consequently triggering ferroptosis in bladder cancer cells and inhibiting the migration ability of bladder cancer cells effectively. This research contributes to a more profound comprehension of nano-drug-biological interactions and provides a prospective outlook on treating bladder cancer by instigating ferroptosis in tumor cells through GSH depletion.
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ACS Nano
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2024
·
IF 15.8
Ze Wang,Xiaojun Ren,Yunfeng Li,Ling Qiu,Dongzhou Wang,Annan Liu,Hao Liang,Lei Li,Bai Yang,Andrew K. Whittaker,Zhongshan Liu,Shunzi Jin,Quan Lin,Tiejun Wang
Insufficient reactive oxygen species (ROS) production and radioresistance have consistently contributed to the failure of radiotherapy (RT). The development of a biomaterial capable of activating ROS-induced apoptosis and ferroptosis is a potential strategy to enhance RT sensitivity. To achieve precision and high-efficiency RT, the theranostic nanoplatform Au/Cu nanodots (Au/CuNDs) were designed for dual-mode imaging, amplifying ROS generation, and inducing apoptosis-ferroptosis to sensitize RT. A large amount of ROS is derived from three aspects: (1) When exposed to ionizing radiation, Au/CuNDs effectively absorb photons and emit various electrons, which can interact with water to produce ROS. (2) Au/CuNDs act as a catalase-like to produce abundant ROS through Fenton reaction with hydrogen peroxide overexpressed of tumor cells. (3) Au/CuNDs deplete overexpressed glutathione, which causes the accumulation of ROS. Large amounts of ROS and ionizing radiation further lead to apoptosis by increasing DNA damage, and ferroptosis by enhancing lipid peroxidation, significantly improving the therapeutic efficiency of RT. Furthermore, Au/CuNDs serve as an excellent nanoprobe for high-resolution near-infrared fluorescence imaging and computed tomography of tumors. The promising dual-mode imaging performance shows their potential application in clinical cancer detection and imaging-guided precision RT, minimizing damage to adjacent normal tissues during RT. In summary, our developed theranostic nanoplatform integrates dual-mode imaging and sensitizes RT via ROS-activated apoptosis-ferroptosis, offering a promising prospect for clinical cancer diagnosis and treatment.
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Drug Design Development and Therapy
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2025
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IF 5.1
Zhida Long,Xiao Yu,Shijia Li,Nuo Cheng,Chenglong Huo,Xuewen Zhang,Shuai Wang
Introduction Oxidative stress is an important cause of acetaminophen (APAP)-induced liver injury (AILI). Sakuranetin (Sak) is an antitoxin from the cherry flavonoid plant with good antioxidant effects. However, whether sakuranetine has a protective effect on APAP-induced liver injury is not clear.Methods Mouse and HepG2 cell models of APAP injury were used to investigate the effect of sakuranetin on AILI and its mechanism. Serum transaminase levels, histological changes, inflammatory mediators, oxidative stress, ferroptosis-related markers and Nrf2 signaling pathway proteins were analyzed.Results Sakuranetin significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as inflammatory factor; increased HepG2 activity and decreased cell death; inhibited ROS production, increased glutathione (GSH) content, expression of Glutathione Peroxidase 4 (GPX4) and Solute Carrier Family 7 Member 11 (SLC7A11), and decreased malondialdehyde and Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4) expression in mice and HepG2 cells after APAP treatment. Further analysis showed that sakuranetin induced the activation of the NFE2 Like BZIP Transcription Factor 2 (Nrf2) signaling pathway in liver tissue and HepG2 cells and promoted the nuclear translocation of Nrf2. Moreover, the hepatoprotective effect of sakuranetin and its inhibitory effect on ferroptosis were significantly attenuated by the Nrf2 inhibitor ML385.Conclusion Sakuranetin alleviates AILI by activating the Nrf2 signaling pathway and inhibiting ferroptosis, and sakuranetin may be a potential therapeutic agent for the treatment of AILI.
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ACS Applied Materials & Interfaces
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2025
·
IF 8.2
Jiazhuo Gong,Yuwei Qiu,Chaojie Yu,Cheng Cao,Xiuqiang Li,Jiajun Lu,Weiqing Zhao,Zhongming Zhao,Haitao Zhang,Fanglian Yao,Hong Sun,Hong Zhang,Junjie Li
Ferroptosis plays a significant role in ischemic heart disease by exacerbating myocardial injury through oxidative stress, iron metabolism disorder, and inflammation. Herein, we develop an injectable hydrogel (HSD/DFO@GMs) with antiferroptosis and antioxidant properties for cardiac repair. The hydrogel is composed of dopamine-grafted oxidized hyaluronic acid, adipic acid dihydrazide grafted hyaluronic acid, and deferoxamine loaded gelatin microsphere, connected via a dynamic Schiff base bond. This hydrogel exhibits a favorable injectability and stable mechanical properties. It effectively chelates Fe2+ and scavenges the reactive oxygen species (ROS), creating a conducive microenvironment for cardiac repair. The dynamic Schiff base bond and gelatin matrix respond to the weakly acidic and MMP-2-rich microenvironment postinjury, enabling on-demand release of DFO in the injured myocardium. In vitro experiments indicate that the hydrogel significantly inhibits the ferroptosis and oxidative stress damage in H9C2 cardiomyocytes under a hypoxia/reoxygenation microenvironment. In an in vivo ischemia–reperfusion model, the HSD/DFO@GMs hydrogel reduces oxidative stress, modulates intracellular labile iron pool levels, and promotes revascularization, ultimately improving cardiac function. Overall, the HSD/DFO@GMs hydrogel provides a new strategy to improve cardiac repair by inhibiting ferroptosis and mitigating oxidative stress damage.
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Scientific Reports
·
2025
·Vol. 15
·期 1
·1-12
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IF 3.9
Wu Zhiwei,Zhang Fan,Yang Kai,He Wenfei
Breast cancer is the leading cause of cancer-related death in women worldwide, and its developmental mechanisms involve complex factors. Recent studies have shown that ferroptosis is closely related to the occurrence and progression of breast cancer. However, the role of circular RNAs (circRNAs) in regulating ferroptosis in breast cancer remains unclear. In this study, we investigated the regulatory role of circSCD1 (hsa_circ_0019512) in breast cancer. We examined the expression of circSCD1 in breast cancer cell lines and explored its impact on cell viability and colony formation. We also evaluated the involvement of circSCD1 in ferroptosis by measuring the levels of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), and intracellular iron. In vivo xenograft experiments were performed to confirm the role of circSCD1 in promoting tumor growth and inhibiting ferroptosis.Furthermore, we investigated the mechanism by which circSCD1 regulates SCD1 protein stability through ubiquitination and identified the interaction between circSCD1 and the deubiquitinase OTUB1. Our results showed that circSCD1 was upregulated in breast cancer cell lines and promoted cell viability and colony formation. Knockdown of circSCD1 increased MDA and ROS levels, decreased GSH levels, and enhanced ferroptosis in breast cancer cells. In vivo, circSCD1 knockdown significantly reduced tumor size and weight, while its overexpression enhanced tumor growth. Mechanistically, circSCD1 interacted with OTUB1 to inhibit the ubiquitination and degradation of SCD1 protein, thereby stabilizing its expression. Rescue experiments demonstrated that SCD1 overexpression partially reversed the effects of circSCD1 knockdown on cell proliferation and ferroptosis. Our findings suggest that circSCD1 plays a crucial role in promoting breast cancer cell growth and inhibiting ferroptosis by regulating SCD1 protein stability. Targeting the circSCD1/OTUB1/SCD1 axis may provide a potential therapeutic strategy for breast cancer treatment.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2025
·
IF 9.7
Qiao-Mei Zhou,Yuan-Fei Lu,Xiao-Yan Yang,Jin-Guo Zhang,Yi-Ning Wang,Wang-Ping Luo,Jin Mao,Jue Hou,Fan Wu,Wei-Lin Wang,Gu-Ping Tang,Hong-Zhen Bai,Ri-Sheng Yu
Hepatocellular carcinoma (HCC) presents formidable therapeutic challenges due to its pronounced metabolic heterogeneity, particularly arising from spatially uneven glucose availability within the tumor microenvironment (TME). To address this, we developed a glutathione (GSH)-responsive, biomimetic hybrid nanoenzyme system (M@GOx/Fe-HMON) composed of hollow mesoporous organosilica nanoparticles co-loaded with glucose oxidase (GOx) and Fe 2+ /Fe 3+ redox pairs, and cloaked in homologous tumor cell membranes for enhanced targeting. In glucose-rich regions, the nanoenzyme orchestrates a GOx-peroxidase (POD) cascade that produces reactive oxygen species (ROS) via the Fenton reaction, leading to ferroptosis through intensified oxidative stress and GSH depletion. Conversely, under glucose-deficient conditions, the nanoenzyme promotes disulfidptosis by aggravating glucose deprivation, depleting nicotinamide adenine dinucleotide phosphate (NADPH), and impairing cystine metabolism, ultimately resulting in actin cytoskeletal collapse. This dual-action platform dynamically adapts to the tumor’s metabolic landscape, selectively inducing ferroptosis or disulfidptosis according to glucose levels, disrupting redox homeostasis and amplifying antitumor efficacy. Notably, this study is the first to integrate ferroptosis and disulfidptosis activation into a single, metabolism-sensitive nanoenzyme system, providing a novel paradigm for exploiting tumor metabolic heterogeneity. Furthermore, the combination of endogenous metabolic regulation with magnetic resonance imaging (MRI)-guided diagnosis introduces an innovative and noninvasive strategy for precision cancer theranostics.
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FREE RADICAL BIOLOGY AND MEDICINE
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2025
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IF 8.2
Wei Deng,Jie Zhao,Xia Wang,Dinggang Li,Mingxin Wang,Xiangqin Zheng,Runchang Wang,Qitong Guo,Peng Zhao,Hao Yan,Lianju Shen,Chunlan Long,Guanghui Wei,Shengde Wu
Di-(2-ethylhexyl) phthalate (DEHP), a commonly used plasticizer, has been demonstrated to possess reproductive toxicity; however, the precise mechanisms underlying this effect have yet to be fully elucidated. This study aimed to investigate the potential mechanisms by which prepubertal DEHP exposure impairs testicular development and to provide possible therapeutic targets. We exposed BALB/c male mice from postnatal days 22–35 to different doses of DEHP (0, 250, and 500 mg/kg/day) and utilized lipid metabolomics and other methods to elucidate the reproductive damage caused by DEHP from a multidimensional tissue-cell-molecule perspective. Our findings indicate that DEHP exposure induces ferroptosis in testicular tissue by remodeling membrane lipid structure, in which the imbalance of phospholipid-polyunsaturated fatty acids (PL-PUFA) and phospholipid-monounsaturated fatty acids (PL-MUFA) playing a crucial role. DEHP exposure altered the expression of ACSL4 and MBOAT2 via HIPPO and androgen receptor pathways, thereby impacting PL-PUFA/PL-MUFA synthesis. In conclusion, this study highlights a link between DEHP-induced reproductive damage and lipid metabolism reprogramming, suggesting new targets for preventing DEHP-induced reproductive toxicity.
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NANOTECHNOLOGY
·
2025
·Vol. 36
·期 30
·305101
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IF 2.8
Gaojian Liu,Wenjing Wen,Xuan Zhao,Yanan Jing,Hao Li,Xulong Fan,ZiXuan Huang,Gaofeng Liang
Breast cancer is the most prevalent fatal cancer among women worldwide and the leading cause of death for women. Ferroptosis is a form of programmed cell death that relies on iron and is non-apoptotic, triggered by the inhibition of the cellular antioxidant system. Photodynamic therapy (PDT) employs photosensitizers to produce reactive oxygen species (ROS), increasing oxidative stress in tumor cells. When combined with ferroptosis, PDT can work synergistically to regulate intracellular redox balance. In this study, we designed engineered nano-erythrocyte membranes for targeted delivery of Chlorin e6 (Ce6) and cisplatin (DDP) to enhance breast cancer treatment. By using mild ultrasound, Ce6 and DDP were co-loaded onto the nano-erythrocyte membranes, combining ferroptosis inducers and photosensitizers to combat breast cancer. To improve targeting capability towards breast cancer, RGD cyclic peptides were modified onto the nano-erythrocyte membranes through a thiol–maleimide coupling reaction. The RGD-modified nano-erythrocyte membranes co-loaded with Ce6 and DDP not only inherited the good stability and significant biocompatibility of red blood cell membranes but also promoted the uptake by breast cancer cells, effectively inducing ferroptosis in these cells. In conclusion, this multifunctional ‘natural’ nanodrug delivery system provides an effective and safe method for PDT combined with ferroptosis for breast cancer treatment.
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Cell Communication and Signaling
·
2025
·Vol. 23
·期 1
·1-21
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IF 8.9
He Qiongyao,He Wu,Ren Yanlin,Wu Wenbin,Dong Hui,Yuan Gang,Ren Huihui,Wang Xinwei,Lu Fuer,Wang Dingkun
Ferroptosis, an iron-dependent form of programmed cell death, is closely associated with tubular damage in diabetic nephropathy (DN). Glutathione peroxidase 4 (GPX4) is an important anti-oxidant enzyme, and plays a crucial role in protecting against ferroptosis. However, the regulatory mechanism of GPX4 expression levels in renal tubular epithelial cells (RTECs) remains elusive. This study reveals that ferroptosis occurs in the late-stage of DN, and the GPX4 level is significantly downregulated in DN patients, animal models and cell models. By applying database predictions, luciferase reporter assays and chromatin immunoprecipitation, we find that vitamin D receptor (VDR) transcription factor promotes GPX4 expression and plays a key role in inhibiting ferroptosis of RTECs. VDR knockout exacerbates ferroptosis in RTECs and worsens renal function, while intraperitoneal injection of VDR agonist paricalcitol significantly improves renal injury. Proteomics analysis suggests that E3 ligase PRPF19 mediates ubiquitination degradation of VDR and is an important therapeutic target for DN. Therefore, through molecular docking, targeted fishing technology using high-performance affinity beads, and surface plasmon resonance (SPR), we screen and identify berberine (BBR) as a novel inhibitor of PRPF19, which offers renal protection by inhibiting VDR degradation and tubular ferroptosis. These findings elucidate the role of ferroptosis in DN renal tubular injury, and suggest that PRPF19 is a promising therapeutic target.
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