ANALYTICA CHIMICA ACTA
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2020
·
IF 5.977
Tingting Niu,Guoxing Yin,Ting Yu,Yabing Gan,Chenye Zhang,Juanjuan Chen,Wei Wu,Haimin Chen,Haitao Li,Peng Yin
Monitoring cellular GSH dynamics is of great value to understand its complex biological functions and related diseases. It still remains challenging to understand the mechanism of GSH dynamics in complex intracellular environment. Herein, a novel fluorescent probe featured with chlorinated coumarin-TCF was exploited for sensing of GSH with high selectivity and high sensitivity. Large fluorescence enhancement at 471 nm was observed upon addition of GSH with large emission distance ( Δλ em = 219 nm). This novel probe was successfully applied to monitor endogenous and exogenous GSH dynamics without interference of other thiols via fluorescence imaging. More importantly, using this probe, low dose reactive oxygen species induced GSH increasement through nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signal pathway in BEL-7402 cells was observed. This novel fluorescent probe has the potential for quantitative monitoring of cellular GSH, which will promote further understanding of its physiological and pathological roles in biological systems.
研究领域:
生物化学
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分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
BIOMATERIALS
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2016
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IF 8.387
Liangliang Dai,Yonglin Yu,Zhong Luo,Menghuan Li,Weizhen Chen,Xinkun Shen,Feng Chen,Qiang Sun,Qingfeng Zhang,Hao Gu,Kaiyong Cai
This study reports a reactive oxygen species (ROS) sensitive drug delivery system based on amphiphilic polymer of poly(propylene sulfide)-polyethylene glycol-serine-folic acid (PPS-mPEG-Ser-FA). The polymer could form homogeneous micelles with an average diameter of around 80 nm through self-assembly, which would then be loaded with the singlet oxygen-generating photosensitizer of zinc phthalocyanine (ZNPC) and anti-cancer drug of DOX. The disassembly of micelles could be triggered by the hydrophobic to hydrophilic transition of the PPS core in response to ROS-induced oxidation in vitro . ZNPC molecules are capable of producing ROS under laser irradiation, which results in the rapid disassembly of micelles and releasing of the anti-tumor drug for tumor therapy under physiological condition otherwise. Moreover, the excessive ROS production deriving from ZNPC synergically induces cells apoptosis. Furthermore, the DOX loaded amphiphilic micelles could be internalized by tumor cells via FA receptor-mediated endocytosis to effectively inhibit the tumor growth in vivo , while with only minimal toxic side effects. The results in vitro and in vivo consistently demonstrate that the light-responsive micelle is a promising biodegradable nanocarrier for on-command drug release and targeted tumor therapy.
研究领域:
药学
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生物医学工程
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纳米技术
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癌症研究
·
药物递送系统
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2020
·
IF 7.727
Xiang-long Tang,Zhen Wang,Yun-yang Zhu,Hong Xiao,Yong Xiao,Sheng Cui,Ben-lan Lin,Kun Yang,Hong-yi Liu
Single reactive oxygen species (ROS)-mediated therapy, photodynamic therapy (PDT) or chemodynamic therapy (CDT) is severely hindered in hypoxic solid tumor . Herein, to address the urgent challenge, a hypoxia-activated ROS burst liposome has been fabricated to achieve synergistic PDT/CDT that is initiated by the structural dissociation of poly(metronidazole) liposome in hypoxic tumor microenvironment (TME). The therapeutic enhancement of our ROS-blasting treatment is simultaneously regulated by external light-initiated PDT and endogenous iron oxide nanoclusters-triggered CDT, which is synergistically boosted and amplified by localized mild hyperthermia under 808/660 nm coirradiation. More importantly, in vitro and in vivo experiments demonstrate that electron-affinic poly(aminoimidazole) product from hypoxia-responsive transition of poly(metronidazole) polymers could efficiently enhance hypoxic cell apoptosis and induce solid tumor ablation. Thus, this work offers a potential hypoxia-activated ROS burst-PDT/CDT strategy with a superior antitumor efficacy, highlighting a promising clinical application.
研究领域:
癌症治疗
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纳米医学
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生物医学工程
·
药学
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DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2022
·
IF 7.31
Fei Jia,Yu Liu,Xinyu Dou,Chuanchao Du,Tianli Mao,Xiaoguang Liu
Osteosarcoma (OS) is the most common malignancy of bone. Liensinine exerts antitumor effects on cancers of the colon, breast, and gallbladder. However, its antitumor activity in OS remains unclear. This study is aimed at investigating the efficacy of liensinine against OS and the underlying mechanism of action. Cell proliferation, apoptosis, and cycle arrest in OS were detected using the Cell Counting Kit-8 (CCK-8), colony formation, and flow cytometry assays, respectively. The production of reactive oxygen species (ROS), glutathione (GSH) and glutathione disulfide (GSSG) concentrations, and mitochondrial membrane potential (MMP) of OS cells were measured by flow cytometry, colorimetry, and JC-1 staining. The expressions of factors related to apoptosis, cell cycle, and activation of the JAK2/STAT3 pathway were determined by Western blotting. To examine the potential role of ROS, an antioxidant (N-acetyl cysteine, NAC) was used in combination with liensinine. In vivo, we generated a xenograft mouse model to assess its antitumor efficacy. Tissue level expressions of factors related to apoptosis and activation of the JAK2/STAT3 pathway were assessed by immunohistochemistry or Western blotting. Liensinine inhibited the proliferation and induced G0/G1 phase arrest and apoptosis of OS cells in a dose-dependent manner. Additionally, liensinine promoted intracellular ROS production, enhanced the GSSG/GSH ratio, and induced MMP loss and ROS-mediated suppression of the JAK2/STAT3 pathway. NAC significantly attenuated the liensinine-induced antitumor activities and activated the JAK2/STAT3 pathway. In vivo, liensinine effectively inhibited the OS growth and promoted apoptosis; however, it had no negative effect on the internal organs. In conclusion, liensinine-induced ROS production could suppress the activation of the JAK2/STAT3 pathway and inhibit the OS growth both in vivo and in vitro. Our findings provided a new rationale for subsequent academic and clinical research on OS treatment.
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DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2018
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IF 2.559
Shuxian Xia,Yinglei Miao,Side Liu
Withaferin A (WA) is an active steroidal lactone derived from the herbal plant Withania somnifera , which exhibits antitumor activity with reactive oxygen species (ROS) modulating in a variety of cancer models, such as breast cancer, lung cancer and pancreatic cancer. However, to the best of our knowledge, the direct effect and mechanism of WA on CRC cells has not been previously determined. The present study investigated the anti-tumor effects of WA on CRC cells in vitro, and explored the mechanisms of action. The flow cytometry was applied for detecting the accumulation of ROS with the treatment of withaferin A. We performed the flow cytometry and western blot to evaluate the withaferin A induced apoptosis and cell cycle arrest in human colon cancer cells. And to verify the ROS accumulation induced mitochondrial dysfunction after the treatment of withaferin A, fluorescence microscope and western blot were applied. WA exerted a dose-dependent cytotoxic effect on HCT-116 and RKO cells. The effect was associated with ROS-mediated cell cycle arrest and the expression of apoptotic proteins. In addition, WA promoted ROS production and decreased mitochondrial membrane potential accompanying with mitochondrial dysfunction. Taken together, these results strongly indicated that WA directly inhibits cell growth and induces apoptosis in CRC cells through ROS-mediated mitochondrial dysfunction and JNKs pathway, and WA may be a promising potential candidate for therapeutic application of CRC.
研究领域:
肿瘤学
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药理学
·
细胞生物学
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DOI
PubMed
高影响因子
Theranostics
·
2020
·
IF 8.579
Xi Chen,Ying Zhao,Wu Luo,Sian Chen,Feng Lin,Xi Zhang,Shijie Fan,Xian Shen,Yi Wang,Guang Liang
Background: Oxidative stress from elevated reactive oxygen species (ROS) has been reported to induce cell apoptosis and may provide a means to target cancer cells. Celastrol is a natural bioactive compound that was recently shown to increase ROS levels and cause apoptosis in cancer cells. However, the underlying mechanism for this cytotoxic action remains unclear and direct molecular targets of Celastrol have not been identified. Methods: Proteome microarray, surface plasmon resonance, isothermal titration calorimetry and molecular simulation were used to identify the molecular target of Celastrol. Binding and activity assays were used to validate the interaction of Celastrol with target protein in cell-free and gastric cancer cell lysates. We then assessed target transcript levels in in biopsy specimens obtained from patients with gastric cancer. Gastric cancer growth-limiting and cytotoxic activity of Celastrol was evaluated in BALB/c nu/nu mice. Results: Our data show that Celastrol directly binds to an antioxidant enzyme, peroxiredoxin-2 (Prdx2), which then inhibits its enzyme activity at both molecular and cellular level. Inhibition of Prdx2 by Celastrol increased cellular ROS levels and led to ROS-dependent endoplasmic reticulum stress, mitochondrial dysfunction, and apoptosis in gastric cancer cells. Functional tests demonstrated that Celastrol limits gastric cancer cells, at least in part, through targeting Prdx2. Celastrol treatment of mice implanted with gastric cancer cells also inhibited tumor growth, associated with Prdx2 inhibition and increased ROS. Analysis of human gastric cancer also showed increased Prdx2 levels and correlation with survival. Conclusion: Our studies have uncovered a potential Celastrol-interacting protein Prdx2 and a ROS-dependent mechanism of its action. The findings also highlight Prdx2 as a potential target for the treatment of gastric cancer.
研究领域:
肿瘤学
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药理学
·
分子生物学
·
癌症治疗
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DOI
PubMed
高影响因子
JCI Insight
·
2022
·
IF 9.484
Jing Yang,Hongxia Li,Chi Zhang,Yafeng Zhou
There is a high prevalence of ventricular arrhythmias related to sudden cardiac death in patients with chronic kidney disease (CKD). To explored the possible mechanism of CKD-related ventricular arrhythmias, a CKD rat model was created, and indoxyl sulfate (IS) was further used in vivo and in vitro. This project used the following methods: patch clamp, electrocardiogram, and some molecular biology experimental techniques. IS was found to be significantly elevated in the serum of CKD rats. Interestingly, the expression levels of the fast transient outward potassium current–related (I to,f -related) proteins (Kv4.2, Kv4.3, and KChIP2) in the heart of CKD rats and rats treated with IS decreased. IS dose-dependently reduced I to,f density, accompanied by the decreases in Kv4.2, Kv4.3, and KChIP2 proteins in vitro. IS also prolonged the action potential duration and QT interval, and paroxysmal ventricular tachycardia could be induced by IS. In-depth studies have shown that ROS/p38MAPK, ROS–p44/42 MAPK, and NF-κB signaling pathways play key roles in the reduction of I to,f density and I to,f -related proteins caused by IS. These data suggest that IS reduces I to,f -related proteins and I to,f density by activating ROS/MAPK and NF-κB signaling pathways, and the action potential duration and QT interval are subsequently prolonged, which contributes to increasing the susceptibility to arrhythmia in CKD.
研究领域:
心脏病学
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肾病学
·
分子生物学
·
电生理学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
An Gao,Fengyu Wang,Xiaonan Cui,Jin Wu,Chunyang Sun,Zhaoxiang Ye
Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising strategy for combination with chemotherapy in cancer treatment. However, the rational design of delivery systems capable of simultaneously inducing ferroptosis, enhancing chemotherapy efficacy, and reducing systemic toxicity remains a substantial challenge. Herein, we developed a reactive oxygen species (ROS)-responsive, ionically crosslinked chitosan/hyaluronan polyelectrolyte nanogel for targeted chemo-ferroptosis combination therapy. In this system, hyaluronic acid (HA) was first esterified with 1,2-bis (2-hydroxyethylthio) ethylene (BE) and subsequently conjugated with methotrexate (MTX) through a ROS-cleavable linkage, yielding an anionic HA- BE -MTX polymeric prodrug. Protonated chitosan (CS) served as the cationic polymeric component, while sodium tripolyphosphate (TPP) further stabilized the nanogel network through ionic crosslinking. Sorafenib (SOR), a ferroptosis inducer, was physically encapsulated during the ionotropic gelation process. The resulting R-NG MS nanogels were designed to maintain colloidal stability under physiological conditions and to undergo ROS-triggered network loosening and drug release in the tumor microenvironment, where oxidative stress is elevated. This dual-delivery system enabled ROS-responsive MTX release and SOR-mediated ferroptosis induction, thereby promoting ROS accumulation, glutathione depletion, GPX4 suppression, lipid peroxidation, and apoptosis in breast cancer cells. In vivo studies demonstrated that R-NG MS efficiently accumulated in 4T1 tumors through prolonged circulation and HA-CD44-mediated tumor targeting, achieving a tumor growth inhibition rate of 75.85% with reduced systemic toxicity compared with free drug treatment. These findings demonstrate that ionically crosslinked CS/HA-based polyelectrolyte nanogels provide an effective and selective platform for ROS-responsive chemo-ferroptosis combination therapy.
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2026
·
IF 7.3
Chengyuan Qian,Yunhua Zhang,Xiaofeng Dang,Yating Shao,Chengyan Chu,Zijian Guo,Chen Xu,Xiaoyong Wang
Modulation of mitochondrial dynamics is a viable strategy for lifespan extension. Reactive oxygen species (ROS) play key roles in aging, acting either as signaling molecules to facilitate longevity-associated processes or as stimulators of oxidative stress, exerting deleterious effects on physiological functions. The hybrid molecule MC1 is designed by integrating melatonin and catechol moieties to reconstruct mitochondrial dynamics and selectively regulate the generation of ROS. MC1 combats cell senescence under oxidative stress and DNA damage, and reprograms the mitochondrial energy metabolism by inhibiting the tricarboxylic acid cycle and glycolysis, while initiating fatty acid oxidation to increase energy production. More importantly, MC1 significantly extends the lifespan of Caenorhabditis elegans, accompanied by an improvement in muscle strength and physiological functions. The lifespan-extending effect of MC1 arises from its intervention in mitochondrial membrane fusion, the electron transport chain, and differential modulation of ROS. Regulating mitochondrial dynamics and ROS production shows great potential for longevity extension.
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产品关联
DOI
PubMed
高影响因子
PLANT JOURNAL
·
2026
·Vol. 127
·期 4
·e71093
·
IF 6.2
Ao Li,Shuo Wang,Xiushuo Liang,Sheng Luo,Honghong Hao,Renjing Wan,Shaowu Xue
Salinity induces the accumulation of reactive oxygen species (ROS) in plants, thereby regulating plant growth and development, including seed germination. However, the molecular mechanisms underlying the regulation of ROS homeostasis in response to salt stress remain largely unknown. Here, we showed that an leucine‐rich‐repeat receptor‐like kinase, REK1, regulates ROS production by phosphorylating the NADPH oxidase respiratory burst oxidase homolog D (RBOHD) in Arabidopsis in response to salt stress. Salt‐induced ROS accumulates extensively in rek1 mutants, causing stress that reduces the seed germination rate of rek1 below that of the wild‐type (Col‐0), resulting in the salt‐sensitive phenotype. Furthermore, REK1 interacts with RBOHD and phosphorylates it at Ser163, thereby regulating its NADPH oxidase activity and influencing ROS production under salt stress. Genetic data revealed that the salt‐sensitive phenotype of rek1 is rescued in rek1 rbohd mutants. In summary, our study revealed a salt stress regulation mechanism that modulates ROS production in Arabidopsis through the REK1‐RBOHD pathway. The study shows that REK1, a member of the leucine‐rich repeat receptor‐like kinase family, increases plant tolerance to salt stress during seed germination by phosphorylating NADPH oxidase respiratory burst oxidase homolog D, thereby regulating its oxidase activity and reactive oxygen species levels.
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LANGMUIR
·
2026
·
IF 4.4
Sehrish Ibrahim,Wensheng Xie,Xiaofeng Li,Guofeng Li,Xing Wang
Engineering interfacial electronic interactions between physically distinct metal oxides without phase transformation, doping, or lattice fusion remains a central challenge of interface science. Conventional Cu2O–ZnO systems rely on heterojunction formation or compositional mixing, whereas carbon-mediated electronic coupling between discrete phases remains largely unexplored. Here, we report strongly electronically coupled carbon-bridged Cu2O/ZnO nanocomposites (Cu2O–C–ZnO NCs) synthesized by incorporating spherical Cu2O and diamond-shaped ZnO nanoparticles into a gallic-acid-derived carbon framework. Structural and compositional analyses confirm the coexistence of crystalline Cu2O and ZnO interlocked in a homogeneous carbon matrix, with oxygenated carbon functionalities verified spectroscopically. X-ray photoelectron spectroscopy reveals binding energy shifts in Cu and Zn core levels, providing direct evidence of interfacial electronic coupling and charge redistribution without lattice fusion or heterojunction formation. This electronic interface coupling helps regulate charge transfer between the oxide materials, allowing the controlled release of metal ions and enhancing the generation of reactive oxygen species. As a functional consequence, the NCs exhibit significant antibacterial activity against Gram-negative and Gram-positive bacteria, as well as substantial antialgal activity against freshwater species. Mechanistic evidence validates that the activity stems from a synergy of phenomena, including controlled ion release, ROS, and membrane damage due to oxidative stress, supported by findings from enzymatic and cellular assays. These results demonstrate that carbon-mediated interfacial electronic coupling is a viable method for controlling the surface reactivity of multicomponent oxide systems with the intact structural integrity of individual components.
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高影响因子
Biomaterials Science
·
2026
·
IF 6.1
Rongjie Gao,Feiyan Chen,Yong Li,Zhengshuai Tang,Jinliang Liu
While combination therapies generally exhibit superior therapeutic outcomes compared to single-modality treatments, current photodynamic–chemodynamic (PDT/CDT) combination strategies remain limited by two major factors: (i) the restricted tissue penetration depth of light and (ii) the insufficient endogenous hydrogen peroxide (H2O2) concentration within the tumor microenvironment (TME), both of which compromise therapeutic efficacy. To overcome these obstacles, we developed an innovative hybrid nanorobot (EcN + UCNPs@mSiO2–MnO2–ZnPc) that integrates engineered Escherichia coli Nissle 1917 (EcN) with orthogonally emissive upconversion nanoparticles (C@3S). Specifically, MnO2 decomposes into Mn2+ under acidic TME conditions, subsequently catalyzing the conversion of H2O2 into cytotoxic hydroxyl radicals (˙OH) and oxygen, which exhibits dual effects of tumor cell eradication and hypoxia alleviation. Meanwhile, C@3S transforms 980 nm laser radiation into blue-violet emission, activating the EcN that preferentially colonizes tumor regions and overexpresses respiratory chain enzyme II (NDH-II), thereby replenishing H2O2 in situ and sustaining chemodynamic therapy (CDT). Additionally, zinc phthalocyanine (ZnPc) is excited by the 808 nm-converted red emission to generate singlet oxygen (1O2), further enhancing reactive oxygen species (ROS) accumulation and amplifying oxidative stress in tumor cells. Collectively, our findings demonstrate significant tumor growth inhibition through this self-amplifying ROS-generation mechanism. This multifunctional hybrid nanorobot offers a promising platform for precision cancer therapy with spatiotemporal controllability.
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