CHEMICAL ENGINEERING JOURNAL
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2025
·
IF 13.2
Yan Gong,Qiurong Sun,Gao He,Jiarui Wang,Dequan Xiao,Lile Dong
Insufficient intracellular Fe 2+ ions availability and hypoxic tumor microenvironment significantly hamper the efficiency of ferroptosis. There is an urgent need for breakthrough research in the development and delivery of ferroptosis inducers and the reprogramming of the immune microenvironment. Herein, Ti 3 FeBi 5 O 15 (TFBO) piezoelectric nanosheets were engineered to amplify ferroptosis and trigger immunogenic cell death via ultrasound (US) activation. TFBO nanosheets feature a narrow bandgap (2.03 eV) and high piezoelectric coefficient (d 33 = 22.1 pm V −1 ), enabling efficient electron-hole separation under US irradiation. Notably, TFBO nanosheets generate an internal piezoelectric field that promotes Fe 3+ to Fe 2+ conversion and ·OH generation from H 2 O under US irradiation, while simultaneously depleting intracellular GSH under US irradiation, leading to lipid peroxidation and GPX4 suppression. Importantly, TFBO nanosheets activate immunogenic cell death (ICD), stimulating antitumor immune responses. Therefore, combined with its high biocompatibility, effective tumor inhibiting performance, and minimal systemic toxicity, TFBO represents a mechanistically distinct and translationally promising ferroptosis amplifier for tumor therapy.
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高影响因子
MATERIALS & DESIGN
·
2025
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IF 7.9
Jingxian Mao,Xueping Huang,Yang Liu,Ying Wang,Dandan Li,Zhuobin Xu,Xuebing Yan,Tingting Liu,Huihui Wang
Both reactive oxygen species (ROS) and ferroptosis are recognized for their pivotal regulatory roles in tumor survival. However, the hypoxic and high glutathione (GSH) environment within tumors presents a significant barrier to these therapeutic strategies. In this study, we have developed a novel gold-doped carbon-dotted nanozyme (Au-CDs) exhibiting multi-enzyme-like activities, which effectively alleviate tumor hypoxia and achieve the self-enhanced combined treatment effect of chemodynamic (CDT) and photodynamic therapy (PDT) independent of oxygen. Furthermore, it effectively depletes GSH to achieve a robust ROS amplifier. The synthesized Au-CDs have demonstrated efficacy in inducing ROS release, promoting lipid peroxidation accumulation and reducing the GSH levels, resulting in the inhibited proliferation of tumor cells in vitro . In a xenograft model, Au-CDs effectively inhibited the tumor growth of nude mice. In terms of molecular mechanism, Au-CDs were able to upregulate transferrin receptor 1 (TFR1) expression and increase the Fe 2+ content, and finally to induce the tumor related ferroptosis, which was more significant in combination with self-enhanced PDT. The biosafety assessment demonstrated Au-CDs had no significant toxicity in the major organs of mice. Taken together, these findings suggested Au-CDs as a novel and safe nanozyme have great potential to be utilized in combination therapies in cancer.
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高影响因子
NEW JOURNAL OF CHEMISTRY
·
2025
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IF 2.5
Hanyu Yao,Ruixuan Ji,Xiaoyi Song,Bin Yang,Yin Lv,Zhong Wei
Ferroptosis, a recently recognized form of non-classical programmed cell death (PCD), leads to impaired cellular structure and integrity due to the accumulation of lipid peroxidation products (LPO). However, single treatment ferroptosis often fails to achieve optimal tumor treatment outcome. Therefore, we constructed a multi-synergistic treatment strategy based on ferroptosis, that is more conducive to tumor therapy. In this study, we constructed a metal organic framework (MOF) loaded with glucose oxidase (GOx) and doxorubicin (DOX), denoted as Fe(Ⅲ)-RSSR@DOX@PEG-GOx. Fe(Ⅲ)-RSSR@DOX@PEG-GOx was synthesized through coordination between Fe3+ and disulfide-containing ligands scavenged GSH and downregulate glutathione peroxidase 4 (GPX4), thereby triggering ferroptosis. The GOx catalyzes glucose into abundant H2O2, promoting the Fenton reaction which results in excessive ROS formation within tumors. The accumulation of ROS can further enhance the process of ferroptosis, while the massive consumption of glucose constitutes a synergistic situation of “starvation treatment”. The smart biomimetic nanoplatform integrates ferroptosis, chemotherapy, and starvation therapy, providing a potential anti-tumor strategy to achieving multi-effect synergistic tumor treatment.
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Science China-Life Sciences
·
2026
·
IF 9.6
Wang Bao,Fu Junpeng,Qian Jian,Wei Yuang,Bao Meiling,Miao Haoqi,Zhao Xinzhe,Shao Kezheng,Song Yuan,Tan Ruoyun,Li Jie,Shao Pengfei
Clear cell renal cell carcinoma (ccRCC) exhibits aberrant lipid synthesis, yet how this metabolic reprogramming influences ferroptosis—a form of regulated cell death driven by lipid peroxidation—remains poorly understood. This study demonstrates that the key lipid transcription factor SREBP1 acts as a master regulator that promotes ccRCC progression by suppressing ferroptosis. Using SREBP1-knockdown cell models, we found that SREBP1 depletion enriches ferroptosis-related pathways and enhances ferroptosis sensitivity, as evidenced by elevated mitochondrial ROS, labile iron pool, PE-OOH levels, and characteristic mitochondrial alterations. Mechanistically, SREBP1 transcriptionally represses the pro-ferroptotic gene ACSL4 while simultaneously activating the lipid-synthesis gene FASN . Rescue experiments revealed that modulating either ACSL4 or FASN alone only partially reverses the ferroptosis phenotype induced by SREBP1 loss, whereas dual manipulation of both genes fully restores ferroptosis resistance. Metabolomic analyses showed that ACSL4 and FASN converge to regulate the cellular PUFAs/MUFAs ratio, which in turn feeds back to modulate SREBP1 nuclear translocation, thereby establishing a self-reinforcing positive-feedback loop. Clinically, low ACSL4 expression correlates with advanced tumor stage and poor patient survival. In vivo, SREBP1 promotes tumor growth by inhibiting ferroptosis via the ACSL4 / FASN axis. Collectively, our findings reveal that SREBP1 drives ccRCC malignancy through a dual-pronged mechanism—repressing ACSL4 and activating FASN—to alter the PUFAs/MUFAs balance and establish a feed-forward loop that sustains ferroptosis suppression. ACSL4 represents a potential prognostic biomarker, and targeting the SREBP1-ACSL4 / FASN axis offers a promising therapeutic strategy for ccRCC.
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
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IF 8.7
Xuyan Hu,Hao Zhuang,Ke Gao,Yaqi Zhu,Fan Gao,Haili Wang,Zijin Zhang,Baoqiang Su,Yubing Zhang,Cailiang Shen
Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents, featuring aggressive tumor growth and early metastasis. Current treatments, including chemotherapy and surgery, are often limited by chemoresistance and postoperative infections. Ferroptosis has emerged as a strategy to overcome chemoresistance, as it is intrinsically iron-dependent, whereas OS often exhibits dysregulated iron metabolism. Halicin, a broad-spectrum antimicrobial known to regulate iron metabolism in bacteria, was found to be a ferroptosis inducer for OS in this study. However, its therapeutic efficacy is likely hampered by rapid systemic clearance and poor tumor retention. Accordingly, we developed Halicin@Gel, an injectable hyaluronic acid hydrogel designed for localized and prolonged release. The structure, injectability, drug release behavior, biocompatibility, antibacterial activity, and antitumor efficacy of this system were characterized and evaluated in vitro and in vivo. Halicin@Gel exhibited excellent antibacterial activity and significantly inhibited OS cell proliferation and migration in vitro. Mechanistically, Halicin@Gel increased intracellular ROS levels and was associated with p38 MAPK activation, as well as ferroptosis- and apoptosis-related changes. In vivo, Halicin@Gel significantly inhibited tumor growth with minimal systemic toxicity, confirming its therapeutic potential. Thus, these findings support Halicin@Gel as a promising localized therapeutic platform with combined antitumor and antibacterial functions for OS treatment.
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高影响因子
TOXICOLOGY
·
2026
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IF 4.6
Jin Chen,Hanwen Hu,Jing Fu,Yaolin He,Hui Zhou,Jingwei Lei,Ming Huang,Jianqi Wang,Anfei Liu,Zhenzhong Liu
Trimethyltin chloride (TMT), a pervasive environmental organic tin pollutant, has been implicated in cardiac injury, though its underlying mechanisms remain unclear. TMT exposure triggers excessive reactive oxygen species (ROS) generation, a key inducer of ferroptosis—a regulated form of cell death driven by iron-dependent lipid peroxidation. NADPH oxidase 4 (NOX4), highly expressed during cardiac development, plays a critical role in myocardial ROS production, while the Keap1/Nrf2 pathway regulates cellular ROS homeostasis. We hypothesized that TMT induces cardiac developmental defects by activating NOX4/Keap1/ROS-mediated ferroptosis. TMT exposure induced cardiac malformations, pericardial edema, and reduced heart rate in zebrafish embryos. Further studies revealed that TMT upregulated nox4 expression in embryonic hearts. Notably, pharmacological inhibition or genetic knockdown of nox4 markedly attenuated TMT-induced cardiac defects. Moreover, nox4 suppression antagonized TMT-triggered dysregulation of the Keap1/Nrf2 axis, ROS overaccumulation, mitochondrial damage, and ferroptosis-related abnormalities—including Fe²⁺ accumulation, elevated lipid peroxidation, and downregulated glutathione peroxidase 4 (GPX4) expression. Crucially, inhibition or knockdown of keap1 similarly mitigated TMT-induced ROS bursts, mitochondrial injury, and ferroptosis progression. Intervention with ferroptosis-specific inhibitors (Liproxstatin-1 and Myricetin) confirmed that ferroptosis directly contributes to TMT-induced cardiac developmental defects. This study demonstrates that TMT induces cardiac malformations by activating ferroptosis via the nox4/Keap1/Nrf2/ROS signaling axis. These findings reveal a novel mechanism underlying TMT cardiotoxicity, provide theoretical insights for assessing TMT exposure as a risk factor for congenital heart disease, and identify potential molecular targets for therapeutic intervention.
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高影响因子
Food & Function
·
2023
·Vol. 14
·期 4
·1884-1896
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IF 6.1
Huiyi Li,Qiqing Weng,Shuai Gong,Weixian Zhang,Jiaqi Wang,Yuqiao Huang,Yuanjun Li,Jiao Guo,Tian Lan
Acetaminophen (APAP)-induced liver injury (AILI) has become a growing public health problem. Ferroptosis, an iron-dependent form of cell death associated with lipid peroxide accumulation, has been recently implicated in AILI. The activation of the Nrf2 signaling pathway is a potential therapy for AILI. Kaempferol (KA), a flavonoid widely existing in edible plants, has been reported to exert profound anti-inflammatory and antioxidant activities. This study aimed to investigate whether KA exerts anti-AILI effects via the Nrf2 signaling pathway. Mice were fasted for 22 h and injected intraperitoneally with APAP (250 mg kg−1) to induce AILI. Mice were pre-injected intragastrically with KA for 2 h followed by APAP injection. The hepatic injury was observed by H&E staining. Biochemical parameters of the serum and liver were measured using kits. KA alleviated hepatic injury and inflammatory response in AILI mice and ameliorated APAP-induced hepatic iron overload and oxidative stress in mice. In addition, the protective effects of KA against APAP-induced hepatotoxicity were examined in L02 cells in vitro. Cell viability was assayed by the CCK8 assay. Mitochondrial reactive oxygen species (ROS) in L02 cells were detected by MitoSox fluorescence. KA reversed the APAP-induced decrease in cell viability and GSH levels and inhibited the accumulation of intracellular ROS. Furthermore, KA activated the Nrf2 pathway and upregulated Gpx4 in mouse livers and L02 cells to inhibit ferroptosis induced by APAP. Finally, molecular docking indicated the potential interaction of KA with Keap1. Taken together, KA ameliorated oxidative stress and ferroptosis-mediated AILI by activating Nrf2 signaling.
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高影响因子
Food & Function
·
2023
·Vol. 14
·期 2
·1087-1098
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IF 6.1
Chengzhu Song,Dongning Li,Jie Zhang,Xiaoyan Zhao
Imatinib mesylate (IMA) belonging to the selective tyrosine kinase inhibitor family has been proven to induce cardiotoxic effects along with therapeutic strategies. Nrf2-dependent ferroptosis has been implicated in the cardiotoxicity induced by IMA. The present study was designed to investigate the protective effects of berberine hydrochloride (Ber) on cardiac injuries induced by IMA and to explore its potential mechanisms. In H9c2 cells, cell viability, the generation of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and labile iron pool (LIP) levels were measured. In a mouse model of IMA-induced cardiomyopathy, serum biomarkers and cardiac tissues were examined. A western blot assay was performed to evaluate the expression of ferroptosis-related proteins in vitro and in vivo. Our results indicated that Ber increased cell viability and MMP and decreased cellular ROS and iron levels in comparison to the IMA group of H9c2 cells. In mice, Ber significantly improved cardiac status and attenuated the level of ferroptosis biomarkers including malonaldehyde (MDA) and iron content. Additionally, Ber downregulated the expression of transferrin receptor (TfR) and P53 and upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1), ferritin heavy chain-1 (FTH1), and glutathione peroxidase 4 (GPX4) in H9c2 cells and mice. The present data indicated that Ber has the potential to protect against IMA-induced cardiotoxicity, partly via inhibiting Nrf2-dependent ferroptosis.
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高影响因子
Biomaterials Science
·
2022
·Vol. 11
·期 2
·542-553
·
IF 7.59
Yang Liu,Jinzhu Chen,Zi He,Huiling Luo,Xinxin Liu,Yanan Sun,Dongtao Ge,Xin Liu,Wei Shi
Ferroptosis induced by iron-dependent accumulation of lipid peroxides (LPOs) has received increasing attention in cancer therapy, especially chemodynamic therapy (CDT). However, the quick annihilation of hydroxyl radicals (˙OH) severely restricts the ˙OH/LPO conversion efficiency, which has become one of the key factors that influences the therapeutic efficacy of ferroptosis-based CDT. Herein, we designed a ˙OH/LPO nano-converter with a high LPO generation efficiency via loading ferrocene (Fc), a green Fenton catalyst, in the phospholipid bilayer of liposome-PEG (Fc-Lp-PEG). Under catalysis with Fc, the over-expressed H2O2 in tumors can be decomposed to ˙OH. The generated ˙OH in situ reacts with unsaturated lipids on the liposome, and is converted into LPOs, which spread the lipid peroxidation chain reaction to the remote membranes of cells and organelles, triggering efficient cancer cell ferroptosis. Systematic in vitro and in vivo therapeutic outcomes showed the high tumor inhibition ratio (74.0%) and the low side effects of Fc-Lp-PEG on 4T1 tumor-bearing mice. This novel strategy for improving the ˙OH/LPO conversion efficiency might provide new insights for the clinical development of ferroptosis-based CDT.
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高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Junfeng Liu,Xi Li,Jiayao Chen,Xiaoting Zhang,Jingpei Guo,Jinyan Gu,Chaoming Mei,Yitai Xiao,Chao Peng,Junbin Liu,Xiaojun Hu,Ke Zhang,Dan Li,Bin Zhou
Hepatocellular carcinoma (HCC) has a poor response to most available systemic therapies due to intrinsic or acquired resistance to apoptosis. Ferroptosis-based therapy is expected to circumvent those limitations. Therefore, the rational design of ferroptosis-based therapies with targeted delivery of ferroptosis inducers for HCC is in need. In this study, we found that arsenic trioxide (ATO) can efficiently induce ferroptosis in HCC cells, and this effect could be reversed by the iron chelator deferoxamine. On this basis, a drug delivery system was constructed to enhance the therapeutic efficacy of ATO by camouflaging ATO-loaded magnetic nanoparticles (Fe3O4) with HCC cell membranes, termed AFN@CM. After AFN@CM treatment, glutathione peroxidase 4 was strongly inhibited and intracellular lipid peroxide species were significantly increased in HCC cells. In addition, enhanced ferroptosis and tumor suppression were observed both in vitro and in vivo. The bio-safety of AFN@CM was also demonstrated by the in vivo toxicity evaluation. In addition, benefiting from the cell membrane coating, AFN@CM showed enhanced accumulation at tumor sites and achieved continuous tumor elimination in the mouse model. In conclusion, AFN@CM exhibited satisfactory therapeutic efficacy in the treatment of HCC and provided a desirable ferroptosis-based strategy for safe and reliable HCC therapeutics.
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高影响因子
Environmental Science-Nano
·
2023
·Vol. 10
·期 2
·640-655
·
IF 7.3
Zuo Wang,Yi Bi,Kemin Li,Zan Song,Chuanying Pan,Shengxiang Zhang,Xianyong Lan,Nicholas S. Foulkes,Haiyu Zhao
Nickel oxide nanoparticles (NiO-NPs) with unique characteristics have been widely utilized in numerous manufacturing processes, which have inevitably led to environmental pollution and health hazards. Previous studies have shown that nanoparticles may enter the central nervous system (CNS) and trigger off various adverse effects, however, the NiO-NPs induced neurotoxic effects as well as the underlying mechanisms remain unclear yet. In the present study, by taking advantage of the zebrafish model system for genetic analyses, in vivo neuroimaging, and neurobehavioral studies, we have investigated how early-life exposure to environmental levels of NiO-NPs (0, 5, 20, 50, 100 mg L−1) affects embryonic development, neurobehavior and neurodevelopment of zebrafish larvae. Our results reveal that the observed neurobehavioral and neurodevelopmental disorders induced by environmental NiO-NPs exposure are closely related to ROS-mediated apoptosis and iron-mediated ferroptosis, the two main forms of programmed cell death which have been strongly implicated in many types of CNS injuries and diseases. Furthermore, pharmacological interventions of apoptosis and ferroptosis pathways via N-acetylcysteine (NAC) and deferoxamine (DFO) respectively, have strongly implicated apoptosis and ferroptosis in these NiO-NPs induced neurotoxic effects. Thus, this study elucidates the potential cellular and molecular mechanisms underlying NiO-NPs induced neurotoxicity, with implications for our understandings as well as pharmacotherapies of the physiologically damaging effects of other environmental nano-pollutants.
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APPLIED SURFACE SCIENCE
·
2022
·
IF 7.392
Ziqi Cao,Di Sun,Hai Hu,Wenxin Li,Ziying Xiong,Maofen He,Shuqi Cai,Yan Fan,Lulu Zheng,Shifei Kang
The exclusive Fenton activity of iron ions has initiated wide investigation into tumor microenvironment-activated tumor therapy owing to the production of toxic ·OH and extra oxygen for chemodynamic therapy (CDT) and photodynamic therapy (PDT) respectively. However, the sensitivity of the labile iron pool (LIP) is unsatisfactory even when iron ions are placed in the tumor microenvironment. Herein, we constructed ferrous oxalate (FeC 2 O 4 ) self-assembled nanorods loaded with a graphitic carbon nitride (g-C 3 N 4 ) photo-Fenton catalyst, which can catalyze H 2 O 2 to continuously generate abundant ·OH under visible light irradiation. The FeC 2 O 4 self-assembled nanorods also dramatically accelerated O 2 production (catalase activity) to improve the PDT of C 3 N 4 . Furthermore, the photo-Fenton catalyst under excitation also open ion channels and release free iron to increase LIP to exploit the joint CDT and PDT. Characterizations proved the self-assembled nanorods outperformed conventional Fenton catalysts in terms of stability, photoelectric response performance and photo-Fenton catalytic ability, which can be ascribed to the optimized band structure and charge isolating capability. Remarkably, the self-assembled nanorods coated with g-C 3 N 4 also showed excellent biocompatibility during the fluorescence tracing cell phagocytosis experiment, suggesting great in-vivo application potential. The results of enhanced generation of reactive oxygen species, reduction of glutathione, consumption of lipid peroxidation, and reduced cell viability verified the typical ferroptosis mechanism of the FeC 2 O 4 /g-C 3 N 4 self-assemble system as-developed. These results demonstrate the great potential of the biocompatible self-assembly photo-Fenton system for rational control of tumor behaviors.
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