JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2024
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IF 9.4
Rui-Rui Zhao,Ju-Hong Wu,Ling-Wu Tong,Jin-Yu Li,Yu-sheng Lu,Jing-Wei Shao
The heterogeneity of hepatocellular carcinoma (HCC) and the complexity of the tumor microenvironment (TME) pose challenges to efficient drug delivery and the antitumor efficacy of combined or synergistic therapies. Herein, a metal-coordinated carrier-free nanodrug (named as USFe 3+ LA NPs) was developed for ferroptosis-mediated multimodal synergistic anti-HCC. Natural product ursolic acid (UA) was incorporated to enhance the sensitivity of tumor cells to sorafenib (SRF). Surface decoration of cell penetration peptide and epithelial cell adhesion molecule aptamer facilitated the uptake of USFe 3+ LA NPs by HepG2 cells. Meanwhile, Fe 3+ ions could react with intracellular hydrogen peroxide, generating toxic hydroxyl radical (·OH) for chemodynamical therapy (CDT) and amplified ferroptosis by cystine/glutamate antiporter system (System X c - ), whcih promoted the consumption of glutathione (GSH) and inhibited the expression of glutathione peroxidase 4 (GPX4). Notably, these all-in-one nanodrugs could inhibit tumor metastasis and induced immunogenic cell death (ICD). Last but not least, the nanodrugs demonstrated favorable biocompatibility, augmenting the immune response against the programmed death-ligand 1 (PD-L1) by increasing cytotoxic T cell infiltration. In vivo studies revealed significant suppression of tumor growth and distant metastasis. Overall, our work introduced a novel strategy for applications of metal-coordinated co-assembled carrier-free nano-delivery system in HCC combination therapy, especially in the realms of cancer metastasis prevention and immunotherapy.
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Bioactive Materials
·
2024
·
IF 18
Yulu Yang,Xianhui Zhang,Yao Yang,Pengfei Gao,Wuzhe Fan,Tao Zheng,Weihu Yang,Yu Tang,Kaiyong Cai
Postmenopausal osteoporosis (PMOP) is a prevalent condition among elderly women. After menopause, women exhibit decreased iron excretion, which is prone to osteoporosis. To design a specific titanium implant for PMOP, we first analyze miRNAs and DNA characteristics of postmenopausal patients with and without osteoporosis. The results indicate that iron overload disrupts iron homeostasis in the pathogenesis of PMOP. Further experiments confirm that iron overload can cause lipid peroxidation and ferroptosis of MSCs, thus breaking bone homeostasis. Based on the findings above, we have designed a novel Ti implant coated with nanospheres of caffeic acid (CA) and deferoxamine (DFO). CA can bind on the Ti surface through the two adjacent phenolic hydroxyls and polymerize into polycaffeic acid (PCA) dimer, as well as the PCA nanospheres with the repetitive 1,4-benzodioxan units. DFO was grafted with PCA through borate ester bonds. The experimental results showed that modified Ti can inhibit the ferroptosis of MSCs in the pathological environment of PMOP and promote osseointegration in two main ways. Firstly, DFO was released under high oxidative stress, chelating with excess iron and decreasing the labile iron pool in MSCs. Meanwhile, CA and DFO activated the KEAP1/NRF2/HMOX1 pathway in MSCs and reduced the level of intracellular lipid peroxidation. So, the ferroptosis of MSCs is inhibited by promoting the SLC7A11/GSH/GPX4 pathway. Furthermore, the remained CA coating on the Ti surface could reduce the extracellular oxidative stress and glutathione level. This study offers a novel inspiration for the specific design of Ti implants in the treatment of PMOP.
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CHEMICAL ENGINEERING JOURNAL
·
2024
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IF 13.3
Luyao Xu,Xiujun Zhang,Wanyu Yang,Haixiang Li,Jiaqi Wang,Lan Wang,Xicheng He,Yan Wang,Xiaoxia Li
Plant phenolic compounds serve as significant natural antioxidants. However, traditional preparation methods face sustainability challenges. In this study, we synthesized a novel deep eutectic solvent (DES) modified core–shell nanomaterial composed of betaine, ethylene glycol and dopamine hydrochloride based on the spatial arrangement formed by the abundant weak interaction forces in the poly(deep eutectic solvent) (PDES). Utilizing the PDES magnetic nanomaterial and combined with ultrasound-assisted matrix solid phase dispersion (UA-MSPD), it was able to efficiently enrich Fructus Choerospondias phenols (FCP) up to 61.468 ± 0.405 mg/g. Density functional theory (DFT) was used to analyze the adsorption mechanism between the material and the target compounds, which involved weak interactions of electrostatics, hydrogen bonds, and π-π stacking, while maintaining the activity of phenols without destroying the molecular structure. Remarkably, the adsorption efficiency of the material remained above 80 % after six repetitions, indicating excellent reusability. FCPs were identified and analyzed using ultra-performance liquid chromatography-tandem triple quadrupole mass spectrometry (UPLC-Q-TOF-MS). The FCP prepared by Fe 3 O 4 @SiO 2 @PDES exhibited superior in vitro antioxidant performance, achieving enrichment and purification in one step. Cell experiment results showed that FCP could scavenge ROS, regulate cytokines, and reduce ferroptosis caused by ultraviolet radiation, making FCP have therapeutic value in practical applications. The technology opens up a new way for the green and sustainable production and enrichment of plant phenolic compounds for anti-aging treatment.
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Redox Biology
·
2025
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IF 11.9
Lu Li,Yu Cao,Xiangsheng Zhang,Jiayi Guo,Ziqiang Lin,Pengyu Zhou,Chuyin Chen,Jiahao Chen,Yike Liu,Danzhi Luo,Jiurong Chen,Yingdong Deng,Peng Sun,Zhiwen Zeng,Jun Zhou
Spinal cord injury (SCI) induced neuropathic pain (NP) remains a major clinical challenge due to persistent neuroinflammation and oxidative stress. We developed an injectable methacrylated and thiolated gelatin hydrogel loaded with quercetin (MSQ) to synergistically scavenge reactive oxygen species (ROS) and inhibit microglial ferroptosis for NP alleviation and neural repair. The MSQ hydrogel exhibited rapid photocrosslinking, sustained quercetin release, and robust ROS scavenging via thiol groups and quercetin, maintaining intracellular redox homeostasis. MSQ attenuated LPS-induced ferroptosis in BV2 microglia by upregulating Nrf2 expression, promoting its nuclear translocation, and activating the Slc7a11/Gpx4 pathway, thereby reducing lipid peroxidation and inflammatory cytokine release. Network pharmacology and molecular dynamics simulations confirmed quercetin's high-affinity binding to Nrf2. In a murine SCI model, MSQ implantation significantly reduced lesion area, suppressed microglial ferroptosis, and decreased pro-inflammatory mediators (TNFα, IL-1β, IL-6), while enhancing neuronal survival (Nissl/NeuN + cells) and axonal regeneration (MAP2/5-HT + expression). Motor functional recovery assays revealed improved BMS scores, gait regularity, and mechanical/thermal pain thresholds in MSQ-treated mice. This study highlights MSQ hydrogel as a multifunctional therapeutic platform that targets ROS homeostasis and microglial ferroptosis via the Nrf2/Slc7a11/Gpx4 axis, offering a promising strategy for post-SCI NP management and neural regeneration.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·735
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IF 12.6
Song Dake,Li Jianing,Zhu Yidan,Hui Qijun,Qi Hengkai,Yu Hanrui,Chen Lin,Qian Yue,Guo Yuanyuan,Wei Minjie,Guan Qiutong,Li Zhenhua
Despite the promise of ferroptosis in cancer therapy, its insufficient potency and off-target toxicity remain significant challenges. Few studies have explored the therapeutic potential of nanoparticle (NP)-mediated active targeting strategies to induce robust ferroptosis in colon cancer (COC) cells effectively. In this study, we developed sialic acid (SA)-targeted NPs by conjugating artesunate (ART) with alanine (Ala) and phenylboronic acid (PBA) to formulate ART-Ala-PBA NPs (AAP NPs). Compared with nontargeted ART-Ala NPs, AAP NPs accumulated significantly within cancer tissues, inhibited tumor growth, and improved the survival rates of mice with COC, while exhibiting minimal toxicity. Mechanistically, AAP NPs induce ferroptosis through the accumulation of reactive oxygen species and the downregulation of the SLC7A11-GPX4 axis. Deep data-independent acquisition (DIA) proteomics revealed a novel suppression of ribonucleotide reductase regulatory subunit M1 (RRM1), which synergizes with canonical ferroptosis pathways to amplify lipid peroxidation. RNA sequencing further indicated that AAP NPs uniquely modulate autophagy-related processes, suggesting a multimodal mechanism distinct from the alterations in amino acid metabolism induced by parental ART formulations. Collectively, AAP NPs represent the first carrier-free nanoassembly leveraging PBA-mediated SA targeting to co-activate ferroptosis via dual ROS/GPX4-RRM1 regulation, offering a translatable paradigm for precision nanotherapy of COC. Graphical abstract
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ANALYTICA CHIMICA ACTA
·
2025
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IF 6
Shizeng Pei,Huiling Wang,Li Wang,Gang Nie,Chunrong Liu
Background Sulfur dioxide (SO 2 ) and lipid droplets (LDs) polarity are critical regulators in various physiological and pathological processes, and the related research has been hampered by the lack of integrated detection tools in biological samples and multi disease models. Results Herein, we presented a dual-responsive fluorescent probe TDTB to concurrently monitor SO 2 and LDs polarity. Based on the D-π-A architecture, TDTB was constructed by integrating hydrophobic triphenylamine (TPA) group for LDs-specific sensing (λ em = 670 nm) with Michael receptor as SO 2 recognition group (λ em = 489 nm). We demonstrated TDTB had typical AIE characteristics and polar-sensitivity, and could specifically target LDs (Pearson's coefficient r = 0.88). Meanwhile, TDTB exhibited remarkable fluorescence enhancement (about 765-fold) with increased SO 2 , as well as excellent selectivity and anti-interference properties in both physiological buffers and cells. Further, with TDTB , we also realized real-time tracking of endogenous SO 2 fluctuations and LDs polarity alteration across cellular, tissues, and in vivo models. Notably, TDTB was successfully applied in pioneering visualization of acute alcoholic liver injury (AALI), diagnosing cancer, inflammation, and ferroptosis. Significance Our research not only provided a versatile tool for decoding SO 2 -LDs polarity crosstalk but also advanced the understanding of their roles in multi-disease pathogenesis, offering new avenues for mechanistic and therapeutic exploration.
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FOOD CHEMISTRY
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2025
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IF 9.8
Chen Liu,Yihong Liao,Meiyi Ning,Hong Chen,Yang Yang,Qian Tang,Daiwen Chen
Instant tea powder is a convenient, shelf-stable product with growing global popularity, yet the impact of cultivar type on its composition and functionality remains underexplored. This study compared two instant green tea powders from green-leaf (ZYQ) and purple-leaf (ZY) cultivars in terms of metabolite profiles, sensory attributes, and anti-inflammatory effects. Metabolomics and sensory evaluation revealed distinct characteristics: ZYQ contained higher levels of epicatechin, proanthocyanidins, total flavonoids, etc., while ZY was enriched in anthocyanin glycosides and EGCG. ZYQ showed greater umami, sweetness, and harmony, whereas ZY exhibited stronger bitterness, astringency, and a purplish-red infusion. Both powders significantly alleviated LPS-induced inflammation in RAW 264.7 macrophages by inhibiting NF-κB and ferroptosis-related oxidative stress, reducing ROS, MDA, iron, and inflammatory mediators. ZY induced stronger upregulation of Nrf2 , Gpx4 , and Txnrd1 , indicating enhanced antioxidant defense. These findings demonstrate that cultivar selection shapes instant tea's flavour and bioactivity, with purple-leaf products offering distinctive functional advantages.
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Frontiers in Pharmacology
·
2020
·
IF 4.225
Tsai Yun,Xia Changbo,Sun Zhongwen
Lung cancer is the most common malignant tumor and is the leading cause of cancer-related deaths worldwide. Extraction of bioactive substances from herbs is considered as an alternative method to traditional treatment. 6-Gingerol is a naturally occurring phenol found in ginger that can be used to treat tumors and suppress inflammation. To determine whether 6-Gingerol can be used as a therapeutic agent for tumors. In this study, tumor-bearing mice were used as an animal model and A549 as a cell model. Western blot was used to detect the expression of autophagy related proteins ubiquitin-specific peptidase 14 (USP14), Beclin1, microtubule-associated protein light chain 3 (LC3) and ferroptosis related proteins nuclear receptor coactivator 4 (NCOA4), ferritin heavy chain 1 (FTH1), transferrin receptor 1 (TfR1), glutathione peroxidase 4 (GPX4), activating transcription factor4 (ATF4) in vivo and in vitro. MTT and EdU were used to detect the viability of A549 cells. H&E and immunofluorescence were used to localize and detect the expression of proteins. The detection of reactive oxygen species was performed using fluorescence probes. It was found that the administration of 6-Gingerol decreased the expression of USP14, greatly increased the number of autophagosomes, reactive oxygen species (ROS) and iron concentration, decreased the survival and proliferation rate of A549 cells, and significantly decreased tumor volume and weight. The results indicate that 6-Gingerol inhibits lung cancer cell growth via suppression of USP14 expression and its downstream regulation of autophagy-dependent ferroptosis, revealing the function and efficacy of 6-Gingerol as a therapeutic compound in A549 and its possible mechanism of action.
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BMC Complementary Medicine and Therapies
·
2025
·Vol. 25
·期 1
·449
·
IF 3.4
Yuan Yue,Sun Jinlong,Raka Rifat Nowshin,Liu Zixuan,Zhang Zhongwei,Xiao Junsong,Wu Hua
Background Severe periodontitis has impacted upwards of 1 billion people worldwide, posing a public health challenge. Porphyromonas gingivalis ( P. gingivalis ) is a keystone pathogen implicated in periodontal dysbiosis and disease progression. Lemongrass essential oil (LEO), extracted from Cymbopogon citratus (DC.) Stapf, has shown clinical benefits in periodontitis management, yet its mechanisms remain poorly understood. Methods Antibacterial and bactericidal activities of LEO against P. gingivalis were evaluated, along with its effects on heme uptake and storage, early biofilm-related phenotypes, mature biofilm development, and transcriptional regulation of virulence-associated genes. Docking simulations were performed to predict interactions between metabolites identified via GC-MS and virulence-related proteins. LEO’s effects on oxidative stress, inflammatory cytokine secretion, and ferroptosis-related gene expression were also evaluated in LPS-induced RAW 264.7 macrophages. Results The antibacterial efficacy of LEO against P. gingivalis was evidenced by a 51.10 ± 2.17 mm inhibition zone, along with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 34.06 and 68.13 µg/mL, respectively. Growth curve analysis showed sustained suppression over 30 h. At 1/4 − 1/2 MIC, LEO inhibited P. gingivalis hemagglutination, hemolysis ( p < 0.05), and heme accumulation. Moreover, biofilm formation was significantly reduced by over 85% at 1/2 MIC though suppression of autoaggregation and hydrophobicity ( p < 0.05). Molecular docking analysis predicted that α -citral (46.41%) and neral (31.58%), the major metabolites of LEO, may act as potential bioactive metabolites. In addition, LEO significantly reduced the levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), notably decreasing TNF-α secretion to 0.82× and 0.66× (MIC and MBC, respectively) relative to the LPS group ( p < 0.05). It also alleviated oxidative stress through slc7a11 upregulation and subsequent glutathione synthesis, leading to restoration of the GSH/GSSG ratio and a reduction in ROS and MDA levels ( p < 0.05). Moreover, LEO downregulated Tfrc expression and decreased Fe²⁺ accumulation ( p < 0.05), suggesting its potential role in restoring iron homeostasis and suppressing ferroptosis-associated markers, such as Ptgs2 . These effects highlight the multifunctional regulatory capacity of LEO during P. gingivalis -LPS-induced inflammatory stress. Conclusion LEO demonstrated multitarget inhibitory effects by attenuating P. gingivalis virulence and regulating macrophage oxidative and iron homeostasis. These findings support its potential as a natural adjunctive or preventive agent in periodontitis therapy.
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Chemical & Biomedical Imaging
·
2024
·
IF 0
Xing Tian,Jiayi Cheng,Lei Yang,Zhanxian Li,Mingming Yu
Hydrogen peroxide and polarity are closely related to many physiological activities and pathological processes. However, near-infrared fluorescent probes that are sensitive to both H2O2 and polarity are still scarce. Herein, we developed the first dual-channel near-infrared fluorescent probe NBO, with an AIE effect, enabling simultaneous monitoring of H2O2 and polarity. The probe presented high sensitivity, high selectivity, and low detection limit for H2O2. It also had high sensitivity to polarity, independent of pH and viscosity, with large Stokes shifts, good photostability, and low cytotoxicity. Moreover, NBO was able to detect both endogenous and exogenous H2O2 as well as polarity fluctuations in vivo as a method to effectively differentiate between cancer cells and normal cells. Importantly, it also could monitor the therapeutic effects of drugs in inflammation and iron-dead cells and mice. Based on NIR emission, NBO could be used as an imaging tool and a way to evaluate the therapeutic effect of drugs for inflammation and ferroptosis.
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APOPTOSIS
·
2024
·Vol. 29
·期 9
·1679-1695
·
IF 6.1
Fan Aoyu,Li Yunpeng,Zhang Yunyan,Meng Wei,Pan Wei,Chen Meixi,Ma Zhongliang,Chen Wei
Prostate cancer (PCa) is one of the most common cancers affecting the health of men worldwide. Castration-resistant prostate cancer (CRPC), the advanced and refractory phase of prostate cancer, has multiple mechanisms of resistance to androgen deprivation therapy (ADT) such as AR mutations, aberrant androgen synthase, and abnormal expression of AR-related genes. Based on the research of the AR pathway, new drugs for the treatment of CRPC have been developed in clinical practice, such as Abiraterone and enzalutamide. However, many areas in this pathway are still worth exploring. In this study, single-cell sequencing analysis was utilized to scrutinize significant genes in the androgen receptor (AR) pathway related to CRPC. Our analysis of single-cell sequencing combined with bulk-cell sequencing revealed a substantial downregulation of AR-regulated AFF3 in CRPC. Overexpression of AFF3 restricted the proliferation and migration of prostate cancer cells whilst also increasing their sensitivity towards enzalutamide, while knockdown of AFF3 had the opposite effect. To elucidate the mechanism of tumor inhibition by AFF3, we applied GSVA and GSEA to investigate the metabolic pathways related to AFF3 and revealed that AFF3 had an impact on fatty acids metabolism and ferroptosis through the regulation of ACSL4 protein expression. Based on correlation analysis and flow cytometry, we can speculate that AFF3 can impact the sensitivity of the CRPC cell lines to the ferroptosis inducer (RSL3) by regulating ACSL4. Therefore, our findings may provide new insights into the mechanisms of drug resistance in CRPC, and AFF3 may serve as a novel prognostic biomarker in prostate cancer.
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CYTOTECHNOLOGY
·
2025
·Vol. 77
·期 2
·1-18
·
IF 1.7
Zhou Yi,Luan Fengwu,Feng Xiaonan,Yu Min,Li Lu,Guo Xiaoyan,Yin Xiaolong
Chronic kidney disease (CKD) often progresses to renal fibrosis, which is characterized by excessive extracellular matrix deposition and is also linked to ferroptosis. The present study investigated how TGF-β1 induces ferroptosis and thereby contributes to renal tubular epithelial cell fibrosis. Bioinformatics was employed to identify the differentially expressed genes relevant to renal fibrosis. An in vitro TGF-β1-induced fibrosis model of HK-2 cells was established, and the cell shape index was calculated. Fer-1, NAC, and PD98059 were utilized for targeted intervention, and their mechanisms were verified by transducing cells with WISP1-targeting shRNA lentivirus. Cell morphology was examined under a microscope, and cells were collected to determine the levels of ferroptosis-related factors (Fe 2+ , MDA, GSH, and LPO). Western blotting was performed to measure the levels of ERK1/2, WISP1, and ferroptosis indicators (GPX4 and hyperoxidized PRDX4). Flow cytometry was performed to determine the ROS levels and the rate of cell ferroptosis. TGF-β1 induced the transformation of HK-2 cells into fibroblast-like cells, leading to increased ROS levels, activation of the ERK1/2-WISP1 signaling pathway, and upregulation of ferroptosis and fibrosis-related factors. However, these effects could be effectively inhibited through pretreatment with Fer-1, NAC, and PD98059 individually, which further validated the involvement of the ERK1/2-WISP1 signaling pathway. In addition, WISP1 knockdown suppressed the cell transformation into fibroblast-like cells as well as the ferroptosis process, thereby reducing the expression levels of ferroptosis and fibrosis-related factors. The present study substantiated the process through which TGF-β1 elicits the production of ROS and triggers ferroptosis via the ERK1/2-WISP1 signaling pathway to facilitate the development of renal tubular epithelial cell fibrosis.
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