Cell Reports
·
2025
·
IF 6.9
Hui Jiang,Yang Qu,Xianjin Kan,Mengqing Yang,Yabin Gong,Ying Liao,Xusheng Qiu,Lei Tan,Cuiping Song,Venugopal Nair,Chan Ding,Yingjie Sun
Peroxisomes are critical organelles that maintain cellular redox homeostasis. Many viruses induce oxidative stress and degrade peroxisomes, but the mechanisms and consequences remain unclear. In this study, we systematically investigate how virus-induced pexophagy regulates peroxisome homeostasis. Using Newcastle disease virus (NDV) as a model, we demonstrate that NDV infection triggers excessive reactive oxygen species (ROS) production, activating the phosphorylation and peroxisomal localization of ataxia-telangiectasia mutated (ATM). Activated ATM promotes the interaction between the peroxisomal receptor PEX5 and the autophagy receptor p62, driving pexophagy. Pexophagy-mediated peroxisome degradation leads to excess active iron and ROS accumulation, contributing to NDV-induced ferroptosis. Notably, this mechanism is shared by other viruses, such as vesicular stomatitis virus and H9N2 avian influenza virus. Our study provides insights into how virus-induced pexophagy disrupts redox homeostasis to promote ferroptosis, highlighting a link between viral infection, peroxisome degradation, and programmed cell death.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2026
·Vol. 11
·期 1
·98
·
IF 81.2
Lin Jundong,Yang Huikang,Zou Zhihao,Deng Lizhi,Cai Xiaoxia,Chen Muqi,Xu Jiaquan,Yin Wenjun,Wen Biyan,Xie Wenjie,Xu Qianfeng,Zhong Guowei,Wu Zhenjie,Chen Yanfei,Zhang Rihong,Tian Weicheng,Zhang Yixun,Long Yusen,Li Yize,Han Zhaodong,Liang Yuxiang,Ye Jianheng,Lu Jianming,Liang Yingke,Dai Qishan,Zou Fen,He Huichan,Zhong Weide,Zhuo Yangjia
Docetaxel (Doc), a widely used chemotherapeutic agent, was limited by suboptimal therapeutic efficacy and dose-limiting systemic toxicity due to the insufficiency of hydrophilicity and tumor-targeting specificity. To address this limitation, we developed an amphiphilic ferrocene-based polymer, PPEGMA- b -PFMMA (PF), to co-encapsulate Doc and the photosensitizer IR808, forming photothermally responsive nanoparticles (NPs) termed P8D NPs. P8D NPs significantly improved the aqueous stability and tumor-specific accumulation of both agents by leveraging a hydrogen peroxide (H₂O₂)-triggered drug release mechanism within the tumor microenvironment. Under near‑infrared (NIR) irradiation, P8D NPs generated substantial heat and a burst of reactive oxygen species (ROS), promoting NPs disintegration and drug release. Mechanistically, Doc induced nuclear to cytoplasmic translocation of HMGB1, while photothermal/photodynamic therapy (PTT/PDT) facilitated the extracellular release of damage-associated molecular patterns (DAMPs) and tumor-associated antigens via ferroptosis and cell membrane rupture. Together, these actions enhanced dendritic cells (DCs) maturation, antigen presentation and cytotoxic CD8⁺ T cell infiltration in tumor, thereby effectively reversing the immunosuppressive tumor microenvironment. Remarkably, this combination strategy not only inhibited the growth of distant tumors but also established long-term anti-tumor immunological memory to prevent recurrence. This study demonstrates that ferrocene-based nanocarrier-mediated PTT/PDT synergizes with Doc to reactivate antitumor immunity through ferroptosis-induced immunogenic cell death (ICD).
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2019
·Vol. 40
·期 10
·1334-1342
·
IF 4.01
Lu Bin,Chen Xiao-bing,Hong Yu-cai,Zhu Hong,He Qiao-jun,Yang Bo,Ying Mei-dan,Cao Ji
Ferroptosis is a newly characterized iron-dependent form of nonapoptotic regulated cell death triggered by lipid reactive oxygen species (LOOH). The dysregulation of ferroptosis is highly related to cancer, and the induction of ferroptosis is also proposed as a potential strategy for cancer therapy. Although several key regulators have been identified that are involved in ferroptosis, the molecular mechanism underlying this process remains largely unknown. Here, we report that Peroxiredoxin-6 (PRDX6) is a bona fide negative regulator of ferroptotic cell death. The knockdown of intracellular PRDX6 significantly enhances LOOH and ferroptotic cell death triggered by ferroptosis inducers (Erastin and RSL-3), which is correlated with the transcriptional activation of heme oxygenase-1. Moreover, overexpression of heme oxygenase-1 enhances both Erastin- and RSL-3-triggered LOOH, suggesting that heme oxygenase-1 mediates PRDX6 silencing-enhanced ferroptosis. More importantly, the application of a specific PRDX6 phospholipase A2 (iPLA2) inhibitor, MJ-33, synergistically enhances the ferroptosis induced by Erastin, suggesting that PRDX6 removes LOOH through its iPLA2 activity. Thus, our findings reveal an essential role of PRDX6 in protecting cells against ferroptosis and provide a potential target to improve the antitumor activity of ferroptosis-based chemotherapy.
研究领域:
癌症生物学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Viruses-Basel
·
2021
·Vol. 13
·期 12
·2383
·
IF 5.048
Huawei Xia,Zeming Zhang,Fuping You
Murine hepatitis virus strain A59 (MHV-A59) was shown to induce pyroptosis, apoptosis, and necroptosis of infected cells, especially in the murine macrophages. However, whether ferroptosis, a recently identified form of lytic cell death, was involved in the pathogenicity of MHV-A59 is unknown. We utilized murine macrophages and a C57BL/6 mice intranasal infection model to address this. In primary macrophages, the ferroptosis inhibitor inhibited viral propagation, inflammatory cytokines released, and cell syncytia formed after MHV-A59 infection. In the mouse model, we found that in vivo administration of liproxstatin-1 ameliorated lung inflammation and tissue injuries caused by MHV-A59 infection. To find how MHV-A59 infection influenced the expression of ferroptosis-related genes, we performed RNA-seq in primary macrophages and found that MHV-A59 infection upregulates the expression of the acyl-CoA synthetase long-chain family member 1 (ACSL1), a novel ferroptosis inducer. Using ferroptosis inhibitors and a TLR4 inhibitor, we showed that MHV-A59 resulted in the NF-kB-dependent, TLR4-independent ACSL1 upregulation. Accordingly, ACSL1 inhibitor Triacsin C suppressed MHV-A59-infection-induced syncytia formation and viral propagation in primary macrophages. Collectively, our study indicates that ferroptosis inhibition protects hosts from MHV-A59 infection. Targeting ferroptosis may serve as a potential treatment approach for dealing with hyper-inflammation induced by coronavirus infection.Keywords:coronavirus;mouse hepatitis virus (MHV);ferroptosis;therapy
研究领域:
病毒学
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Chemistry Frontiers
·
2021
·Vol. 5
·期 10
·3813-3822
·
IF 6.482
Haifeng Sun,Zhonghe Zhang,Xiaoyu Kang,Qiong Dai,Aixin Song,Jingcheng Hao,Jiwei Cui
Biologically-derived nanoparticles (NPs) are an emerging type of drug carrier in the field of biomedicine due to their unique biological and physicochemical properties. However, the preparation of biologically-derived NPs often requires complex procedures and/or organic solvents, which may reduce versatility in amenable functionalization strategies and suitability for potential biological applications. Herein, we report a green and facile strategy for the scalable synthesis of biologically-derived NPs from mung beans (MBs) and demonstrate an example application in combination cancer therapy. The MB NPs (MBNs) are mainly composed of proteins, polysaccharides, polyphenols, and flavonoids. Doxorubicin (DOX) and metal ions (i.e., Fe2+) can be easily loaded into MBNs, which show their potential as agents for chemo-ferroptosis combination therapy and magnetic resonance imaging. The study establishes a promising strategy to engineer functional NPs of potential interest for biomedical applications including bio-imaging and therapeutic delivery.
研究领域:
生物医学工程
·
纳米技术
·
癌症治疗
·
药物递送系统
·
磁共振成像
✓ 已验证
产品关联
DOI
高影响因子
Small
·
2023
·Vol. 19
·期 16
·2207544
·
IF 13.3
Yan Xu,Weitao Yang,Yi Han,Kexin Bian,Weiwei Zeng,Liangwen Hao,Hui Wang,Yingsheng Cheng,Peijun Wang,Bingbo Zhang
The chemical generation of singlet oxygen ( 1 O 2 ) by the MoO 4 2− -catalyzed disproportionation of hydrogen peroxide (H 2 O 2 ) has been widely applied in numerous catalytic processes; however, such molybdate ions cannot be administered for redox-based cancer therapeutics. This work reports the albumin-mediated biomimetic synthesis of highly active molybdenum sulfide (denoted MoB) nanocatalysts that mediate the simultaneous generation of 1 O 2 and superoxide anion (O 2 •− ) from H 2 O 2 , which is relatively abundant in malignant tumors. The MoB-catalyzed reactive oxygen species (ROS) are able to activate the ferroptosis pathway and cause lipid peroxidation for efficient cancer therapy. Furthermore, for the first time, the catalytic activity of MoB is visualized in situ. Moreover, a catalytic imaging modality based on MoB is developed for specific imaging of inflammation diseases without background interference. Therefore, this study presents a biomimetic strategy toward Mo-based nanocatalysts for ROS-facilitated tumor ferroptosis and catalytic imaging.
研究领域:
癌症治疗
·
生物化学
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·
IF 7
Ting Chen,Jie Yang,He Zhao,Dajian Li,Xiaoyong Luo,Zhiyu Fan,Biye Ren,Yuepeng Cai,Renfeng Dong
Ferroptosis is a non-apoptotic form of cell death that is dependent on the accumulation of intracellular iron that causes elevation of toxic lipid peroxides. Therefore, it is crucial to improve the levels of intracellular iron and reactive oxygen species (ROS) in a short time. Here, we first propose ultrasound (US)-propelled Janus nanomotors (Au–FeOx/PEI/ICG, AFPI NMs) to accelerate cellular internalization and induce cancer cell ferroptosis. This nanomotor consists of a gold–iron oxide rod-like Janus nanomotor (Au–FeOx, AF NMs) and a photoactive indocyanine green (ICG) dye on the surface. It not only exhibits accelerating cellular internalization (∼4-fold) caused by its attractive US-driven propulsion but also shows good intracellular motion behavior. In addition, this Janus nanomotor shows excellent intracellular ROS generation performance due to the synergistic effect of the “Fenton or Fenton-like reaction” and the “photochemical reaction”. As a result, the killing efficiency of actively moving nanomotors on cancer cells is 88% higher than that of stationary nanomotors. Unlike previous passive strategies, this work is a significant step toward accelerating cellular internalization and inducing cancer-cell ferroptosis in an active way. These novel US-propelled Janus nanomotors with strong propulsion, efficient cellular internalization and excellent ROS generation are suitable as a novel cell biology research tool.
研究领域:
生物医学工程
·
纳米技术
·
癌症研究
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2022
·
IF 18.027
Ke Li,Chuanchuan Lin,Menghuan Li,Kun Xu,Ye He,Yulan Mao,Lu Lu,Wenbo Geng,Xuemin Li,Zhong Luo,Kaiyong Cai
Ferroptosis is a recently discovered route of regulated cell death that offers the opportunities for the treatment of chemotherapy-resistant tumor indications, but its efficacy can be affected by the glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) antioxidant mechanisms, posing significant challenges for its clinical translation. In this study, we report a Cu-tetra(4-carboxyphenyl)porphyrin chloride(Fe(III)) (Cu-TCPP(Fe)) metal organic framework (MOF)-based nanosystem for the efficient incorporation of Au nanoparticles (NPs) and RSL3, which can demonstrate enzyme-like activities to universally suppress the antiferroptotic pathways in tumor cells for amplifying ferroptotic damage. Herein, Cu-TCPP(Fe) MOF nanosheets were integrated with Au NPs via in situ nucleation and loaded with RSL3 via π–π stacking, which were eventually modified with polyethylene glycol (PEG) and iRGD for tumor-targeted drug delivery. Specifically, the Au NPs can demonstrate glucose oxidase-like activities for efficient glucose depletion, thus disrupting the pentose phosphate pathway to impede reduced glutathione (GSH) biosynthesis and prevent the recycling of coenzyme Q10 (CoQ10) to CoQ10H2, while Cu species can oxidize GSH into oxidized glutathione (GSSG). These nanocatalytic activities can lead to the simultaneous inhibition of the GPX4/GSH and FSP1/CoQ10H2 pathways and cooperate with the GPX4-deactivating function of RSL3 to cause pronounced ferroptotic damage, thereby providing a strong rationale for the application of ferroptosis therapy in the clinic.
研究领域:
癌症生物学
·
纳米技术
·
治疗学
·
细胞死亡机制
✓ 已验证
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
·
药理学
·
治疗学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-17
·
IF 14.7
Wang Huirui,You Xiaona,Wang Jingcheng,Chen Xinyi,Gao Yinghui,Wang Mengmeng,Zhang Wenru,Zhang Jiaozhen,Yu Yang,Han Bo,Qi Mei,Liu Xiaohui,Lou Hongxiang,Dong Ting
Hemolysis drives susceptibility to lung injury and predicts poor outcomes in diseases, such as malaria and sickle cell disease (SCD). However, the underlying pathological mechanism remains elusive. Here, we report that major facilitator superfamily domain containing 7 C (MFSD7C) protects the lung from hemolytic-induced damage by preventing ferroptosis. Mechanistically, MFSD7C deficiency in HuLEC-5A cells leads to mitochondrial dysfunction, lipid remodeling and dysregulation of ACSL4 and GPX4, thereby enhancing lipid peroxidation and promoting ferroptosis. Furthermore, systemic administration of MFSD7C mRNA-loaded nanoparticles effectively prevents lung injury in hemolytic mice, such as HbSS-Townes mice and PHZ-challenged 7 C −/− mice. These findings present the detailed link between hemolytic complications and ferroptosis, providing potential therapeutic targets for patients with hemolytic disorders.
研究领域:
分子生物学
·
细胞生物学
·
药理学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
Cell Death & Disease
·
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
·
生殖医学
·
药理学
·
细胞生物学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
Translational Cancer Research
·
2026
·Vol. 15
·期 3
·171
·
IF 2.1
Yan Zhang,Lu Lu,Qiuyu Zhao,Aiyu Ma,Meihua Jin,Xu Wang,Yuzhong Yang,Xuan Meng,Yiping Sun,Jinhua Zheng,Xiang Zheng
Background Lysosomal-associated protein transmembrane 5 (LAPTM5) is a transmembrane protein predominantly localized to late endosomes and lysosomes, with preferential expression in hematopoietic cells. Ferroptosis is an iron-dependent, non-apoptotic form of programmed cell death (PCD) that is driven by the lethal accumulation of lipid peroxides. Many studies have shown that ferroptosis is dependent on autophagy. Lipophagy is a selective form of autophagy by degrading lipid droplets (LDs) within autophagic vesicles to regulate lipid balance. Lipophagy can promote RAS-selective lethal 3 (RSL3)-induced ferroptosis. However, whether LAPTM5 regulates lipophagy to sensitize glioma cells to ferroptosis remains to be explored. Therefore, the objective of our study was to evaluate the potential role of LAPTM5 in ferroptosis. Methods The expression profile of LAPTM5 in human glioma tissues was analyzed by using The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases, and immunohistochemistry. Glioma cells were treated with ferroptosis inducer erastin, and then the cell viability, glutathione (GSH), and malondialdehyde (MDA) were detected. Lipophagy was tested by laser confocal microscopy and proteins expression were detected by western blot. Results Elevated expression of LAPTM5 was observed in glioma tissues compared to normal brain tissues, and its high expression level was associated with poorer patient prognosis. LAPTM5 promoted lipophagy in glioma cells. LAPTM5 enhanced the sensitivity of glioma cells to ferroptosis inducer erastin, while suppression of lipophagy inhibited LAPTM5-mediated sensitization to erastin. Conclusions The finding that glioma cells with high LAPTM5 expression were more sensitive to ferroptosis inducers suggests that glioma patients with high LAPTM5 expression may be more responsive to ferroptosis-inducing therapies.
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）