BIOMATERIALS
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2025
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IF 12.9
Yuanlin Wang,Yaqian Han,Jingshi Li,Zhaotong Wang,Kai Li,Tiancheng Bai,Lei Wang,Ye Sun,Chunying Chen,Miao Yu
Ferroptosis serves as a pivotal mechanism in diverse clinical chemotherapeutics and physiological processes, profoundly impacting tumor metabolism and the tumor microenvironment. Recently, the immunosuppression induced by ferroptosis has raised major concerns regarding tumor recurrence upon ferroptosis-based antitumor therapies. However, due to the lack of cell specificity, the antitumor and immunosuppressive effects in ferroptosis are inherently intertwined. Herein, we address the conflicting challenges between immunosuppression and antitumor efficacy in ferroptosis-based therapy by enabling cell-specific ferroptosis, thereby targeting tumors while sparing immune cells. By employing a specially designed nanoagent, i.e. , ferrous selenide half-shell-covered gold, we induce notable upregulation of glutathione peroxidase 4 (GPX4) and downregulation of prostaglandin E2, leading to an increase in CD 4+ and CD 8+ T cell populations and intense antitumor immune responses. Despite the elevated level of GPX4, significant tumor cell ferroptosis is achieved, which is further promoted by the agent's photothermal and photocatalytic effects. Consequently, long-term immunological memory is established, yielding a long-lasting and recurrence-free antitumor efficacy spanning at least 200 days post-treatment. This work unlocks an avenue to balance immunosuppression reversal with tumor inhibition in ferroptosis-based therapies, providing promising prospects for antitumor therapies facing immunological hurdles in the tumor microenvironment.
研究领域:
肿瘤学
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免疫学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2025
·
IF 3.5
Xiaofeng Ma,Wang chen,Zhihao Hu,Like Xie,Zhaobing Li,Huan Liu,Zili Li,Zhentao Jiang,Jiangwei Huang,Changrong Jiang,Ke Huang,Sujun Xiao
Background and aims The anthracycline chemotherapeutic agent doxorubicin (DOX) is widely used to treat cancer. However, DOX carries a high risk of adverse effects such as cardiovascular events. The aim of this study was to explore the role of Trim65 in DOX-induced cardiotoxicity (DIC) and its underlying mechanisms. Methods and Results Cellular studies were performed by exposing H9c2 cells (rat cardiomyocytes) to DOX. H9c2 cells were infected with lentivirus encoding negative control (LV-NC) or Trim65 (LV-Trim65). C57BL/6J mice were exposed to adeno-associated virus 9 (AAV9) containing cTnT promoter-encoded Trim65 sequence (AAV-Trim65) or AAV9 negative control sequence (AAV-NC) via tail vein injection. Furthermore, the following analysis were performed: cell viability, intracellular ROS production and lipid peroxidation. Echocardiography was used to measure the heart function of the mice. qPCR and western blotting were used to assess the expression of Trim65, p53, SLC7A11, and GPX4. According to our study, Trim65 expression was significantly downregulated in DIC. Overexpression of Trim65 exhibited considerable protection against to DIC, confirmed by both in vitro and in vivo experiments. In DOX-treated mice, mitochondria deformation was observed in the heart, as well as a high level of lipid peroxidation (signs of ferroptosis) and iron content, which were mitigated by overexpression of Trim65. Mechanistically, our study confirmed that DOX reduced the Trim65-mediated ubiquitination of p53, ultimately inhibiting the degration of p53. We also found that Trim65 mitigated DOX-induced ferroptosis via p53. Conclusion Collectively, our data demonstrated that Trim65 inhibits ferroptosis by degrading p53, thereby alleviating DIC. Therefore, Trim65 could be a promising target for the treatment of DIC.
研究领域:
分子生物学
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心血管病学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Jian Xiao,Nana Feng,Qiushi Li,Xianghui Cao,Qingqing Huang,Biyu Zhou,Zhenrui Fan,Liping Wei,Yang Liu
Ferroptosis is gaining attention as a potential cancer immunotherapy strategy, as it can stimulate antitumor responses by enhancing dendritic cell (DC) activation and the infiltration of cytotoxic T cells (CTLs). However, cancer cells often develop resistance to ferroptosis, reducing the effectiveness of existing treatments. This study demonstrates a novel mitochondria-targeted ferroptosis inducer, designated mitoFePDA@R, which is engineered to achieve a “closed-loop” cancer immunotherapy strategy of ferroptosis induction, antitumor immune activation, and ferroptosis enhancement. In this strategy, mitoFePDA@R is designed to release Fe 2+ and the mitoGPX4 inhibitor RSL3 within tumor mitochondria, thereby effectively inducing ferroptosis and activating strong antitumor immune responses. Additionally, interferon γ ( IFN-γ) released from CTLs inhibits GSH synthesis, which further enhances the ferroptosis sensitivity of tumor cells to form a “closed-loop” strategy. In vitro studies indicated that mitoFePDA@R induced strong ferroptosis in tumor cells by accumulating lipid peroxides (LPO) in mitochondria (which lacks mitochondria targeting). Animal studies confirmed that mitoFePDA@R effectively triggered ferroptosis and activated subsequent antitumor immune responses, leading to significant tumor growth inhibition. This provides a viable and effective strategy for ferroptosis-associated cancer immunotherapy.
研究领域:
肿瘤学
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免疫学
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细胞生物学
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DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2024
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IF 3.7
Xiuhao Yu,Shaokun Chen,Hailin Wang
Chlorobenzoquinones (CBQs) are a class of emerging water disinfection byproducts that pose significant risks to public health. In this study, we found that three CBQs (tetrachloro-1,4-benzoquinone, 2,5-dichloro-1,4-benzoquinone, and 2-chloro-1,4-benzoquinone) can significantly aggravate cell death caused by Ras-selective lethal small molecule 3 (RSL3). Further study showed that the cell death caused by CBQs, either alone or in combination with RSL3, was related to iron accumulation and GPX4 inactivation, suggesting the occurrence of ferroptosis. Furthermore, reactive oxygen species are found to play a potential key role in mediating the toxicity of CBQs in CBQs and RSL3-induced ferroptosis. These findings will be helpful in understanding the toxic mechanism of CBQs to mammalian cells.
研究领域:
毒理学
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细胞生物学
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环境科学
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公共卫生
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-15
·
IF 14.7
Jiang Jun,Yang Lili,Xie Qianqian,Liu Xi,Jiang Jie,Zhang Jie,Zhang Shuping,Zheng Huizhen,Li Wenjie,Cai Xiaoming,Liu Sijin,Li Ruibin
Ferroptosis is a promising strategy for cancer therapy, with numerous inhibitors of its braking axes under investigation as potential drugs. However, few studies have explored the potential of activating the driving axes to induce ferroptosis. Herein, phosphatidylcholine peroxide decorating liposomes (LIP PCPO ) are synthesized to induce ferroptosis by targeting divalent metal transporter 1 (DMT1). LIP PCPO is found to boost lysosomal Fe 2+ efflux by inducing cysteinylation of lysosomal DMT1, resulting in glutathione peroxidase 4 (GPX4) suppression, glutathione depletion and ferroptosis in breast cancer cells and xenografts. Importantly, LIP PCPO induced ferroptotic cell death is independent of acquired resistance to radiation, chemotherapy, or targeted agents in 11 cancer cell lines. Furthermore, a strong synergistic ferroptosis effect is observed between LIP PCPO and an FDA-approved drug, artesunate, as well as X rays. The formula of LIP PCPO encapsulating artesunate significantly inhibits tumor growth and metastasis and improves the survival rate of breast cancer-bearing female mice. These findings provide a distinct strategy for inducing ferroptosis and highlight the potential of LIP PCPO as a vector to synergize the therapeutic effects of conventional ferroptosis inducers.
研究领域:
癌症生物学
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药理学
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治疗学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2025
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IF 9.6
Chenfeng Qiao,Ziying Sun,Faheem Muhammad,Wenli Gong,Jintao Lin,Jie Lv,Xi Cheng,Yuxiang Fei,Nuo Xu,Ya Xie,Ruiyang Jiang,Chenguang Lin,Haoyu Yang,Zhongyang Lv,Zheng Wang,Yuan Liu,Zhihao Lu,Xiang Gu,Zhaofeng Zhang,Chunqing Hu,Hanwen Zhang,Jia Meng,Xiaojiang Yang,Dongquan Shi,Hui Wei,Nirong Bao
The global prevalence of tendinopathy (TP) is steadily increasing, resulting in functional impairments in tendons across individuals of all ages. Excessive accumulation of reactive oxygen species (ROS) plays a pivotal role in the development of TP, which compromises tendon repair and integrity through oxidative stress. This process is often accompanied by ferroptosis—a newly recognized form of iron-dependent programmed cell death. This study explores ruthenium oxide (RuO 2 ) hollow nanospheres as an effective nanozyme to address oxidative damage and ferroptosis in type I collagenase-induced TP. In vitro experiments show decreased mRNA levels of inflammatory biomarkers in tenocytes, while western blot analysis and immunofluorescence reveal reduced extracellular matrix degradation after RuO 2 treatment. In the TP model, the RuO 2 nanozyme therapy and improves tendon fiber arrangement, alleviates pain, and increases type I collagen expression while preventing matrix degradation. These findings suggest that the RuO 2 nanozyme possesses significant antioxidant and anti-inflammatory properties, providing protective effects on tenocytes by ROS scavenging and countering ferroptosis, indicating its potential for treating TP.
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产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
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2023
·Vol. 14
·期 5
·1-15
·
IF 9
Zhang Shenghui,Liu Qin,Chang Mengyuan,Pan Ying,Yahaya Badrul Hisham,Liu Yanli,Lin Juntang
Chemotherapy was conventionally applied to kill cancer cells, but regrettably, they also induce damage to normal cells with high-proliferative capacity resulting in cardiotoxicity, nephrotoxicity, peripheral nerve toxicity, and ovarian toxicity. Of these, chemotherapy-induced ovarian damages mainly include but are not limited to decreased ovarian reserve, infertility, and ovarian atrophy. Therefore, exploring the underlying mechanism of chemotherapeutic drug-induced ovarian damage will pave the way to develop fertility-protective adjuvants for female patients during conventional cancer treatment. Herein, we firstly confirmed the abnormal gonadal hormone levels in patients who received chemotherapy and further found that conventional chemotherapeutic drugs (cyclophosphamide, CTX; paclitaxel, Tax; doxorubicin, Dox and cisplatin, Cis) treatment significantly decreased both the ovarian volume of mice and the number of primordial and antral follicles and accompanied with the ovarian fibrosis and reduced ovarian reserve in animal models. Subsequently, Tax, Dox, and Cis treatment can induce the apoptosis of ovarian granulosa cells (GCs), likely resulting from excessive reactive oxygen species (ROS) production-induced oxidative damage and impaired cellular anti-oxidative capacity. Thirdly, the following experiments demonstrated that Cis treatment could induce mitochondrial dysfunction through overproducing superoxide in GCs and trigger lipid peroxidation leading to ferroptosis, first reported in chemotherapy-induced ovarian damage. In addition, N-acetylcysteine (NAC) treatment could alleviate the Cis-induced toxicity in GCs by downregulating cellular ROS levels and enhancing the anti-oxidative capacity (promoting the expression of glutathione peroxidase, GPX4; nuclear factor erythroid 2-related factor 2, Nrf2 and heme oxygenase-1, HO-1). Our study confirmed the chemotherapy-induced chaotic hormonal state and ovarian damage in preclinical and clinical examination and indicated that chemotherapeutic drugs initiated ferroptosis in ovarian cells through excessive ROS-induced lipid peroxidation and mitochondrial dysfunction, leading to ovarian cell death. Consequently, developing fertility protectants from the chemotherapy-induced oxidative stress and ferroptosis perspective will ameliorate ovarian damage and further improve the life quality of cancer patients.
研究领域:
肿瘤学
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生殖医学
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药理学
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细胞生物学
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毒理学
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DOI
PubMed
高影响因子
TOXICOLOGY
·
2020
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IF 4.099
Xi Zhao,Zhenhua Liu,Jie Gao,Hu Li,Xiaorong Wang,Yinchuan Li,Fei Sun
Busulfan is commonly used for cancer chemotherapy, nevertheless it cause male infertility via damaging the germ cells. Therefore, the underlying mechanism should be explored. In the present study, we demonstrated for the first time that ferroptosis was involved in busulfan-induced oligospermia in mice. Mice were given testicular injection of busulfan on both sides at the dose of 4 mg/kg body weight to establish the model of oligospermia. Four weeks later, the results showed that busulfan-treated mice exhibited decreased sperm concentration and motility, along with features of typical ferroptosis in testis, such as increased malondialdehyde (MDA) content and prostaglandin-endoperoxide synthase (PTGS2) mRNA expression, and decreased NADPH content. Inhibition of ferroptosis by ferrostatin-1 (Fer-1) or deferoxamine (DFO) partially alleviated busulfan-induced oligospermia in mice. Additionally, we also revealed that busulfan treatment induced spermatogenic cells ferroptosis by down-regulating nuclear factor-E2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4) expressions, and decreasing iron efflux through reduction of ferroportin 1 (FPN1) expression. Fer-1 or DFO obviously reversed busulfan-induced ferroptosis by increasing Nrf2, GPX4 and FPN1 expressions. Furthermore, after activation of Nrf2 by sulforaphane, sperm concentration and motility in busulfan-treated mice increased, accompanied by enhanced expressions of GPX4 and FPN1. These findings imply that busulfan-induced ferroptosis might be mediated via inhibition of Nrf2-GPX4 (FPN1) signaling pathway, and highlight that targeting ferroptosis serves as a potential strategy for prevention of busulfan-induced damage and male infertility.
研究领域:
药理学
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生殖生物学
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毒理学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2023
·
IF 5.9
Jin-Yang Liu,Na Liu,Yue Wu,Xiao-Min Ning,Wen-Chao Zhang,Jing Qian
To improve the treatment efficiency of ferroptosis and accurately monitor the therapy process, we developed small-sized upconversion nanoparticles (UCNPs) by a simple one-step solvothermal method. On this basis, a facile strategy is reported to construct mesoporous SiO2-coated UCNPs as the nanocarrier to load dual drugs of MnO2 and methylene blue (MB) photosensitizer for hypoxic tumor theranostic. Due to the components of high charge elements, the synthetic NaErF4:Yb,Gd,Eu@mSiO2/MnO2/MB@FA (UPSMF/MB, FA = folic acid) exhibited radiosensitization function. Emitting strong red upconversion luminescence (UCL) excited the encapsulated MB to initiate photodynamic therapy (PDT). In addition, UPSMF/MB released green UCL imaging in vivo, so as to trace drug distribution and achieve accurate theranostic. In tumor microenvironment, the loaded MnO2 possessed catalase-like (CAT) catalytic activity, which could effectively decompose excessive H2O2 into O2, thus alleviating hypoxia in the tumor area and promoting PDT and radiotherapy (RT) to generate reactive oxygen species (ROS). Furthermore, MnO2 had excellent glutathione peroxidase (GPx)-like activity, which could effectively decompose intracellular over-expressed glutathione (GSH), thus causing lipid peroxide (LPO) accumulation and inducing ferroptosis. In situ ROS generation by PDT and RT further promoted the accumulation of intracellular LPO. Cytotoxicity assay revealed that the apoptosis rate of UPSMF/MB promoted by RT and PDT was 79.76%, which was 46% higher than that of solo ferroptosis induced by UPSMF. Notably, in vivo results illustrated that the tumor inhibition rate of UPSMF/MB could be increased to 83.4% under the triple effects of RT, PDT, and ferroptosis with negligible side effects to normal tissues. This work paves a way to enhance the efficacy of ferroptosis-based cancer therapy by associating PDT with RT.
研究领域:
癌症研究
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纳米技术
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诊疗一体化
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生物医学工程
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2023
·
IF 6.8
Yan Wang,Yue Zhang,Jinglong Xue,Leqiang Gao,Xiangyang Li,Moxuan Zhao,Dong Zhao,Xianqing Zhou
Decabromodiphenyl ether (BDE-209) is an environmental toxin. Increasing evidence showed that BDE-209 exposure induced liver injury, but the mechanism still remains unknown. The present study explored the effect and mechanism of ferroptosis on hepatotoxicity triggered by BDE-209 in vivo and in vitro . In vivo experiment, ICR mice were exposed to BDE-209 for 50 days, and then recovered for 50 days; HepG2 and L02 cells were treated with BDE-209 or/and ferrostatin-1 (Fer-1) for establishing in vitro model. In vivo , the results showed that BDE-209 accumulated in liver and induced liver damage, increased Fe 2+ and MDA contents, and blocked the activation of SLC7A11/GSH/GPX4 pathway in liver; BDE-209 also activated IKK/IκB/NF-κB pathway and elevated inflammatory cytokines levels in liver after exposure for 50 days. After BDE-209 stopping exposure 50 days, the severity of liver damage, ferroptosis and inflammatory response were still higher than the corresponding control group. In vitro , ferroptosis inhibitor Fer-1 rescued ferroptotic damage and attenuated cell death in BDE-209-treated HepG2 and L02 cells. In addition, Fer-1 reversed the activation of IKK/IκB/NF-κB pathway and the increase of pro-inflammatory cytokines levels in BDE-209-treated HepG2 and L02 cells. Together, the above results suggested that BDE-209 induced tissue damage and inflammatory response by activating ferroptosis through increasing iron-dependent lipid peroxidation and blocking the activation of SLC7A11/GSH/GPX4 pathway in liver, indicating that ferroptosis is a potential mechanism for BDE-209-induced hepatotoxicity.
研究领域:
毒理学
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肝病学
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细胞生物学
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环境科学
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DOI
PubMed
高影响因子
Phytochemistry Letters
·
2023
·
IF 1.7
Yu-Chen Chen,Qiong Zheng,Hui Lu,Yi-Xin Zhuang,Ting-Ting Gong,Lie-Feng Ma,Zha-Jun Zhan
A new flavonoid glycoside bearing an unusual furan ring, epimedokoreanin F ( 1 ), was isolated from Epimedium brevicornu , along with 17 known flavonoids ( 2−18 ). The structures of these flavonoids were identified based on interpretation of spectroscopic data and comparison with literature data. Biologically, compounds 1−4 exhibited significant neuroprotective effects on the model of RSL3-induced ferroptosis in HT22 cells. Among them, compound 1 displayed the best activity with EC 50 values of 0.95 μ M, and can be used as lead compound for the development of neuroprotective agent to treat neurological diseases .
研究领域:
药理学
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神经科学
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生物化学
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植物化学
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产品关联
DOI
高影响因子
Journal of Orthopaedic Surgery and Research
·
2023
·Vol. 18
·期 1
·1-15
·
IF 2.6
Xue Xiang,Dai Tianming,Chen Junyan,Xu Yangyang,Yang Zhenyu,Huang Jian,Xu Wuyan,Li Siming,Meng Qingqi
Background Osteoarthritis (OA) is a prevalent disease plaguing the elderly. Recently, chondrocyte ferroptosis has been demonstrated to promote the progression of OA. Peroxisome proliferator-activated receptor-γ (PPARγ) is an important factor in maintaining cartilage health. However, the relationship between PPARγ and chondrocyte ferroptosis in OA and its mechanism is completely unclear.Methods We established a surgically induced knee OA rat model to investigate PPARγ and chondrocyte ferroptosis in OA. Rat knee specimens were collected for Safranin O/Fast Green staining and immunohistochemical staining after administered orally placebo or pioglitazone (PPARγ agonist) for 4 weeks. We used RSL3 to establish a chondrocyte ferroptosis model cultured in vitro to study the role of PPARγ activation toward ferroptosis, mitochondrial function, and PTEN-induced putative kinase 1 (Pink1)/Parkin-dependent mitophagy. GW9662 (PPARγ antagonist), Mdivi-1 (mitophagy inhibitor), and chloroquine (mitophagy inhibitor) were employed to investigate the mechanism of PPARγ-Pink1/Parkin-dependent mitophagy in the inhibition of ferroptosis.Results We found that PPARγ activation by pioglitazone attenuated not only OA but also inhibited the expression of the ferroptosis marker acyl-CoA synthetase long-chain family member 4 (ACSL4) at the same time in rats. Furthermore, in vivo and in vitro data indicated that PPARγ activation restored Pink1/Parkin-dependent mitophagy, improved mitochondrial function, inhibited chondrocyte ferroptosis, and delayed the progression of OA.Conclusion sThe present study demonstrated that PPARγ activation attenuates OA by inhibiting chondrocyte ferroptosis, and this chondroprotective effect was achieved by promoting the Pink1/Parkin-dependent mitophagy pathway.
研究领域:
骨科
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
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