IET Nanobiotechnology
·
2023
·Vol. 17
·期 4
·387-395
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IF 2.3
Wei Li,Chang Liu,Sichuan Wang,Naifeng Liu
Atherosclerosis is a progressive inflammatory disease characterised by excessive lipid accumulation and inflammatory cell infiltration and is the basis of most cardiovascular diseases and peripheral arterial diseases. Therefore, an effectively targeted delivery system is urgently needed to deliver ferroptosis-specific inhibitors to the site of arterial plaque and the inflammatory microenvironment. Inspired by the fact that neutrophils can be recruited to arterial plaques under the action of adhesion molecules and chemokines, the authors developed a neutrophil membrane hybrid liposome nano-mimetic system (Ptdser-NM-Lipo/Fer-1) that delivers Ferrostatin-1 (Fer-1) to the atherosclerotic plaque effectively, which is composed of Fer-1-loaded Ptdser-modified liposomes core and neutrophils shell. Fer-1 was released at the AS plaque site to remove reactive oxygen species (ROS) and improve the inflammatory microenvironment. In vitro ROS clearance experiments have shown that 50 μmol/ml Fer-1 can significantly remove ROS produced by H 2 O 2 -induced MOVAS cells and Ptdser-NM-Lipo/Fer-1 revealed a 3-fold increase in the inhibition rate of ROS than free Fer-1 in induced-RAW264.7, demonstrating its superior ROS-cleaning effect. Based on the interaction of adhesion molecules, such as vascular cell adhesion molecule 1, ICAM-1, P-selectin, E-selectin, and chemokines released in the inflamed site, the aorta in NM-Lipo-treated mice displayed 1.3-fold greater radiant efficiency than platelet membrane-Lipo-treated mice. Meanwhile, due to the modification of the Ptdser, the aorta in Ptdser-NM-Lipo/Fer-1-treated mice exhibited the highest fluorescence intensity, demonstrating its excellent targeting ability for atherosclerosis. Therefore, we present a specific formulation for the treatment of atherosclerosis with the potential for novel therapeutic uses.
研究领域:
医学
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生物工程
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药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Hanjing Lu,Min Li,Wenxuan Fan,Zhao Li,Ji Cheng,Rui Liu,Pan Xu,Ding Luo,Jinghua Li,Xiaoran Liu
Sepsis-associated acute lung injury (ALI) is a critical clinical problem owing to the complex interactions between inflammation and oxidative stress. It is often associated with high mortality rates and a lack of therapeutic options. To simultaneously combat the interconnected inflammatory and oxidative stress pathways in sepsis-associated ALI, we designed near-infrared (NIR)-responsive nanomedicine by co-loading ferroptosis inhibitor Ferrostatin-1 (Fer-1) with Prussian blue nanozymes (denoted as Fer-1@PB) to achieve synergistic therapy and enhanced efficacy. Fer-1@PB combines the multi-enzyme mimetic properties of PB nanoparticle-based nanozyme (PBzyme) for reactive oxygen species (ROS) scavenging and the ferroptosis-inhibitory function of Fer-1 with spatiotemporally controlled burst release under NIR irradiation. The 0.05), and the conclusion of colloidal stability remains completely unchanged. All the above revisions are limited to typographical adjustments, wording accuracy, and minor typo corrections. No experimental data, results, figures, or cistance. Sincerely, Xiaoran Liu (on behalf of all authors) Corresponding author"?> Fer-1@PB nanozymes exhibited strong therapeutic efficacy in cellular and animal sepsis-related ALI models, with an increased survival rate, reduced pulmonary edema and histopathological damage, and recovery of lung function. Mechanistic investigations using transcriptomic analysis (RNA-seq) and experimental validation revealed that the therapeutic effects were mediated by the modulation of the CXCL2/ARF6/NCF1 signaling axis. This study introduces Fer-1@PB as a highly efficient and biosafe nanotherapeutic approach for ALI via synergistic anti-oxidative and anti-inflammatory effects. It also outlines a new molecular mechanism of action, yielding new insights into the precise nanomedicine for inflammatory lung disease.
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Tianfeng Yang,Suyu Zhang,Kun Nie,Xiuhong Peng,Jian Huo,Xiao Fu,Yanmin Zhang
Although ferroptosis as an emerging way exhibits tremendous promising in the therapy of hepatocellular carcinoma (HCC), the novel therapeutic agents targeting ferroptosis are still scarce. In our previous study, we found that the natural products toosendanin (TSN) possessed significant anti-proliferative efficacy by regulating WW domain-containing oxidoreductase (WWOX) in HCC. However, there is very limited understanding about TSN-induced ferroptosis, and the role of WWOX in ferroptosis has not been studied. In present study, we investigated the effect and underlying molecular mechanisms of TSN in WWOX-mediated ferroptosis in HCC. We found that TSN induced ferroptosis in HCC cells and its effect was dependent on WWOX. RNA-seq and RT-qPCR assay identified that TSN significantly increased spermidine/spermine N1-acetyltransferase 1 (SAT1) expression while decreased solute carrier family 40 member 1 (SLC40A1) expression, which play vital roles in ferrous ion transport. Further dual-luciferase reporter assay and Co-IP assay revealed that TSN-induced WWOX activation controlled the transcriptional activity of p53 and NF-E2-related factor 2 (NRF2) by regulating their interaction. Meanwhile, IF assay and WB assay confirmed that TSN increased the nuclear distribution of p-WWOX and p-p53 dimers, but impeded the nuclear translocation of NRF2 by inducing its ubiquitination degradation, ultimately regulating the transcription of their downstream target genes. In addition, the results from cell viability assay and the tumor xenograft model verified that co-treatment of TSN, ML385 (NRF2 inhibitor), and MIRA-1 (p53 activator) could effectively inhibit HCC cells growth in the presence of Fer-1 (ferroptosis inhibitor) in vitro and in vivo. Overall, our study contributes to the necessary understanding of the molecular mechanisms of WWOX-mediated ferroptosis regulation, and identifies TSN as a potential therapeutic agent targeting ferroptosis for HCC.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2022
·
IF 7.129
Wenyu Miao,Lingling He,Yong Zhang,Xiaoyu Zhu,Yangming Jiang,Pengpeng Liu,Tao Zhang,Chunqi Li
Glucocorticoids (GCs) have been widely detected in the aquatic system. However, the hazardous effects of GCs on aquatic organisms were underestimated, and the mechanisms of GCs-induced toxic effects in fish were largely unknown. The zebrafish larvae at 3 dpf were exposed to dexamethasone (DEX) for 48 h, and the toxic effects and the underlying mechanisms were investigated in the current study. The T cells were ablated in zebrafish larvae after being treated with 1, 3, 10, 30 and 100 μM of DEX for 48 h. In addition, osteoporosis was induced and the regeneration of the caudal fin was inhibited, by 48 h-exposure to 10, 30 and 100 μM of DEX. The transcriptomic analysis, biochemical parameters and gene expression profiles revealed that ferroptosis possibly contributed to the DEX-induced toxic effects in zebrafish larvae. Finally, Fer-1 treatment partially attenuated the DEX-induced T cell ablation, but not osteoporosis in zebrafish larvae. Taken together, the current study proved the toxic effects of DEX on zebrafish larvae, and elucidated that ferroptosis was involved in DEX-induced toxicity, providing strong evidence for the toxic effects of GCs on aquatic organisms.
研究领域:
水生毒理学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
Journal of Natural Medicines
·
2024
·
IF 2.5
Cao Yongyi,Wang Yu,Li Yueyang,Liu Sihan,Wang Lizhe,Zhou Li,Zhu Ting
Ferroptosis is a unique programmed cell death driven by iron-dependent phospholipid peroxidation. Tumor cells that escape from the conventional therapies appear more sensitive to ferroptosis. Therefore, it is extremely urgent to find safe and efficient active ingredients that induce ferroptosis in tumor cells. Herein, we identified that angelic acid, as a potent anti-tumor active ingredient in Angelica sinensis , profoundly sensitizes CRC cells to ferroptosis via a natural compound library screen. We revealed that angelic acid treatment is sufficient to predispose CRC cells to ferroptosis phenotype, evidenced by malondialdehyde (MDA) accumulation, lipid peroxidation, and upregulation of ferroptosis-associated markers CHAC1 and PTGS2, which is abolished by ferroptosis inhibitor Fer-1. Moreover, the results of network pharmacology showed that NRF2 is critical for angelic acid-mediated CRC cell ferroptosis. Mechanistically, angelic acid exerted its ferroptosis induction via directly binding and facilitating the degradation of NRF2. In addition, the syngeneic mouse models revealed that angelic acid boosts CRC cell sensitivity to ferroptosis inducer sulfasalazine with essentially no toxicity in vivo. Collectively, our findings highlighted a previously unrecognized anti-tumor mechanism of angelic acid and represented an appealing therapeutic strategy for CRC treatment. Graphical abstract
研究领域:
肿瘤学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2024
·
IF 10.5
Yuge Zhao,Weimin Yin,Zichen Yang,Jiuyuan Sun,Jiao Chang,Li Huang,Liangyi Xue,Xiaoyou Zhang,Hui Zhi,Shiyu Chen,Nana Chen,Yongyong Li
Transforming macrophages into the anti-inflammatory M2 phenotype could markedly strengthen inflammatory bowel disease (IBD) treatment, which is considered as a promising strategy. However, the high ferroptosis sensitivity of M2 macrophages, which decreases their activity, is a major stumbling block to this strategy. Therefore, promoting M2 polarization while simultaneously inhibiting ferroptosis to tackle this challenge is indispensable. Herein, a calcium‑carbonate (CaCO 3 ) mineralized liposome encapsulating a ferroptosis inhibitor (Fer-1) was developed (CaCO 3 @Lipo@Fer-1, CLF). The CaCO 3 mineralized coating shields the liposomes to prevent the release of Fer-1 in circulation, while releasing Ca 2+ in the acidic-inflammatory environment. This released Ca 2+ promotes M2 polarization through the CaSR/AKT/β-catenin pathway. The subsequently released Fer-1 effectively upregulates GSH and GPX4 , scavenges reactive oxygen species , and inhibits ferroptosis in M2 macrophages. In vivo, CLF improved the targeting efficiency of IBD lesions (about 4.17-fold) through the epithelial enhanced permeability and retention (eEPR) effect and enhanced IBD therapy by increasing the M2/M1 macrophage ratio and inhibiting ferroptosis. We demonstrate that the synergistic regulation of macrophage polarization and ferroptosis sensitivity by this mineralized nanoinhibitor is a viable strategy for IBD therapy.
研究领域:
纳米技术
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药学
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炎症
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胃肠病学
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DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2023
·
IF 8.9
Dongxu Wang,Kai Yin,Yue Zhang,Hongmin Lu,Lulu Hou,Hongjing Zhao,Mingwei Xing
Endemic fluorosis (EF) has been listed as one of the serious public health problems in many countries. Long-term exposure to high fluoride can lead to severe neuropathological damage to the brain. Although long-term research has revealed the mechanism of some brain inflammation caused by excessive fluoride, the role of intercellular interactions, especially immune cells, in brain damage is still unclear. Fluoride can induce ferroptosis and inflammation in the brain in our study. A co-culture system of neutrophil extranets and primary neuronal cells showed that fluoride can aggravate neuronal cell inflammation by causing neutrophil extranets (NETs). In terms of the mechanism of action, we found that fluoride leads to the opening of calcium ion channels by causing neutrophil calcium imbalance, which in turn leads to the opening of L-type calcium ion channels (LTCC). Extracellular free iron enters the cell from the open LTCC, leading to neutrophil ferroptosis, which releases NETs. Blocking LTCC (nifedipine) rescued neutrophil ferroptosis and reduced the generation of NETs. Inhibition of ferroptosis (Fer-1) did not block cellular calcium imbalance. In summary, our study explores the role of NETs in fluoride-induced brain inflammation and suggests that blocking calcium channels may be one of the possibilities to rescue fluoride-induced ferroptosis.
研究领域:
神经科学
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免疫学
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毒理学
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细胞生物学
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2023
·
IF 4.3
Qiwen Feng,Yumeng Liu,Liping Zou,Mengying Lei,Changhong Zhu,Wei Xia
Fluorene-9-bisphenol (BHPF) is an emerging global endocrine-disrupting chemical found in numerous household products as a substitute of bisphenol A. Many studies have reported various toxicities associated with BHPF. However, the effect of BHPF on male reproduction, particularly on the structural integrity of the blood testis barrier (BTB) in mice, has not yet been extensively studied. Ferroptosis , a newly identified form of cell death, occurs in the testicular tissue following exposure to BPA, affecting male fertility. We investigated whether ferroptosis plays a role in BHPF-induced testicular damage. The findings indicated that BHPF exposure led decreases in serum testosterone (T) concentration and sperm concentration and motility in mice. Furthermore, BHPF disrupted the BTB by interfering with key BTB-related proteins, including Cx43, β-catenin, and ZO-1. Moreover, BHPF induced ferroptosis through the induction of lipid peroxidation, iron overload, oxidative stress , and mitochondrial dysfunction in the testicular tissue. Inhibition of ferroptosis using Fer-1 mitigated the BHPF-induced damage to the BTB and ferroptosis in TM4 cells. Overall, our findings indicated the detrimental effects of BHPF on male reproductive function in mice, suggesting ferroptosis as a mechanism underlying testicular damage.
研究领域:
毒理学
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生殖生物学
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内分泌学
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DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Kai Yuan,Yiqi Yang,Yixuan Lin,Feng Zhou,Kai Huang,Shengbing Yang,Weiqing Kong,Fupeng Li,Tianyou Kan,Yao Wang,Caiqi Cheng,Yakun Liang,Haishuang Chang,Jie Huang,Haiyong Ao,Zhifeng Yu,Hanjun Li,Yihao Liu,Tingting Tang
The specific mechanisms underlying bacteria-triggered cell death and osteogenic dysfunction in host bone marrow mesenchymal stem cells (BMSCs) remain unclear, posing a significant challenge to the repair of infected bone defects. This study identifies ferroptosis as the predominant cause of BMSCs death in the infected bone microenvironment. Mechanistically, the bacteria-induced activation of the innate immune response in BMSCs leads to upregulation and phosphorylation of interferon regulatory factor 7 (IRF7), thus facilitating IRF7-dependent ferroptosis of BMSCs through the transcriptional upregulation of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4). Moreover, it is found that intervening in ferroptosis can partially rescue cell injuries and osteogenic dysfunction. Based on these findings, a hydrogel composite 3D-printed scaffold is designed with reactive oxygen species (ROS)-responsive release of antibacterial quaternized chitosan and sustained delivery of the ferroptosis inhibitor Ferrostatin-1 (Fer-1), capable of eradicating pathogens and promoting bone regeneration in a rat model of infected bone defects. Together, this study suggests that ferroptosis of BMSCs is a promising therapeutic target for infected bone defect repair.
研究领域:
细胞生物学
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干细胞研究
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组织工程
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再生医学
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生物医学工程
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传染病学
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产品关联
DOI
PubMed
高影响因子
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