ACS Applied Materials & Interfaces
·
2024
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IF 8.3
Shiyan Li,Xuwei Shang,Haiya Lou,Zixu Wang,Yihe Qiu,Shanshan Xiang,Fangying Yu,Hong Yuan
The immunosuppressive tumor environment, characterized by elevated redox levels, significantly impairs the effectiveness of oxidation and the immune response. Here, an electron-accepting-inspired glycopolymer-based nanoreactor (chitosan-grafted nitrobenzene nanoparticles) CNP employing hypoxia-activated group nitrobenzene was constructed to realize cascade bilateral regulation of ferroptosis and immune activation by intervening antioxidant systems. The as-prepared CNP could consume nicotinamide adenine dinucleotide phosphate (NADPH) in the hypoxia-response process, allowing it to be involved in the recycling of glutathione (GSH) and thioredoxin (Trx). This ultimately affects redox homeostasis, leading to reduced GSH levels, increased reactive oxygen species (ROS), and inhibition of (glutathione peroxidase 4) Gpx4. By taking advantage of the sensitivity difference between tumor cells and dendritic cells (DCs) to the ferroptosis inducer erastin (Er) based on varying xCT expression levels, we developed Er-loaded nanoparticles CNP/Er. These nanoparticles not only enhance ferroptosis in 4T1 cells through Gpx4 inhibition by CNP but also promote DC maturation by utilizing CNP’s hypoxia-responsive mechanism to increase ROS levels. The CNP/Er was believed to be an ideal candidate for bilateral regulation of ferroptosis and immune activation in one nanoreactor.
研究领域:
肿瘤学
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生物材料学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Plants-Basel
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2025
·Vol. 14
·期 9
·1354
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IF 4.1
Guoying Yuan,Dan Wang,Chaoguang Yu,Jianfeng Hua,Yunlong Yin,Tingting Chen
DNA methylation plays a crucial role in regulating the developmental processes of plants. Particularly, it is closely associated with the development of embryogenic cells (EC) and somatic embryos (SE). In this study, we investigated the effects of 5-azaCytidine (5-azaC) treatment on somatic embryogenesis proliferation and maturation ofTaxodiumhybrid ‘zhongshanshan’. The results showed that the callus proliferation was inhibited when the concentration of 5-azaC exceeded 30 μM, while treatment with 5 μM 5-azaC improved the maturation rate and expedited the process of SE formation. It was also noted that 5-azaC influenced somatic embryogenesis during the second week of embryo induction, substantially enhancing the maturation rate of somatic embryos and the germination rate ofTaxodiumhybrid ‘zhongshanshan’. Furthermore, the analysis revealed that treatment with 5-azaC resulted in elevated levels of H2O2, SOD, POD, and AsA during the cotyledonary embryo period inTaxodiumhybrid ‘zhongshanshan’, indicating its potential to promote somatic embryogenesis by regulating redox homeostasis. This study concluded that 5-azaC could improve the efficiency of somatic embryogenesis inTaxodiumhybrid ‘zhongshanshan’, as well as provide a solid foundation for investigating the effects of 5-azaC on somatic embryogenesis in other conifer species.
研究领域:
植物学
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遗传学
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发育生物学
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产品关联
DOI
PubMed
高影响因子
CHEMISTRY-A EUROPEAN JOURNAL
·
2025
·
IF 3.7
Zhibin Ren,Xiaoying Liu,Guanghao Lv,Xiaiting Wang,Jingli Wang,Wei Wu,Xingyi Li,Jiaqing Wang
Graphical The conjugation of a polyphenolic antioxidant with a small peptide generates a self-assembled nanodrug, which suppresses ocular inflammation by attenuating oxidative stress in mitochondria after escaping from lysosome. As an investigation of anti-inflammation by the mitochondrial localization of antioxidant, this work establishes a foundation by regulating cellular redox balance for developing drug delivery systems in the treatment of ocular disorders. External environments ( e. g ., pollutants, irritants, ultraviolet radiation, etc ) probably activate oxidative stress on the ocular surface, further leading to inflammatory responses and cellular apoptosis. For treating ophthalmic diseases, one of the strategies is to regulate oxidative stress through antioxidants. Here we conjugate a polyphenolic antioxidant drug ( i. e ., caffeic acid) with a small peptide of protein tag to generate a peptide-drug conjugate as a nanodrug. With a self-assembled ability to form nanoparticles, the nanodrug mainly enters human corneal epithelial cells (HCEC) by caveolin-mediated endocytosis, succeeds lysosomal escape, and achieves mitochondrial localization of caffeic acid. Revealed by free radical scavenging experiments, the nanodrug shows considerable antioxidant capacities. In mouse leukemia cells of monocyte macrophage (RAW 264.7) induced by lipopolysaccharide (LPS), the nanodrug inhibits various pro-inflammatory cytokines ( e. g ., NO, IL-6, and TNF-α) by up-regulating the expression of anti-apoptotic protein ( e. g ., Bcl-2). As an investigation of alleviating oxidative stress by the mitochondrial localization of antioxidant, this work may establish an experimental foundation for the regulation of cellular redox balance, as well as provide different insights for the clinical development of antioxidant drug delivery systems in the treatment of ocular disease.
研究领域:
药理学
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眼科
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产品关联
DOI
PubMed
高影响因子
ACS Applied Polymer Materials
·
2022
·
IF 4.855
Fan Yang,Chenggang Song,Ruixuan Ji,Xiaoyi Song,Bin Yang,Yin Lv,Zhong Wei
Disruption of the balance of cellular redox can increase the cellular concentration of reactive oxygen species (ROS), which leads to oxidative stress-induced apoptosis in cancer cells, therefore minimizing the toxic effects on normal cells. However, this strategy is incomplete in programmable anticancer drug delivery. On the basis of this strategy, we designed, synthesized, and successfully functionalized an amphiphilic copolymer [poly(ethylene glycol) monomethyl ether (mPEG)-b-poly(hydroxyethyl methylacrylate)(PHEMA))-g-SS-hydroxybenzenoborate pinanol ester(HPBAe)/hydroxyethylferrocene (Fc)] that can form stable micelles in water and effectively load the hydrophobic drug doxorubicin (DOX). 1H NMR was used to confirm the structure of the polymers. Transmission electron microscopy (TEM) revealed that the blank or drug-loaded micelles were spherical. Blank micelles displayed negligible cytotoxicity. Ferrocene reacted with H2O2 to form hydroxyl radicals (·OH) through a Fenton or Fenton-like reaction for an enhanced antioxidant ability of cancer cells. H2O2-induced self-destruction of PHEMA can then release quinone methide (QM), which depletes glutathione (GSH) and suppresses the antioxidant capacity of tumor cells. This process can effectively attack cancerous cells through the synergistic effects of DOX, thus maximizing the therapeutic impact. Confocal microscopy also displayed that the drug could be efficiently delivered and released by micelles. Finally, the nano drug loading system containing ferrocene and pinacol phenylborate can actively increase the level of ROS in 4T1 cells and effectively kill 4T1 cells. This amphiphilic copolymer micelle is a stimuli-responsive nanomaterial and a promising therapeutic approach for cancer.
研究领域:
生物化学
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癌症治疗
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材料科学
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DOI
高影响因子
TALANTA
·
2021
·
IF 6.057
Zhen-Cai Xu,Yu-Feng Ge,Kai-Yong Chen,Min-Hua Liu
Sulfur dioxide (SO 2 ) plays an extremely important role in the basic processes of physiology and pathology. As an antioxidant , SO 2 can maintain the redox homeostasis in the cell. Excessive inhalation of SO 2 would lead to irreparable respiratory damage, resulting in respiratory diseases , neurological disorders , and even cardiovascular disease. Thus, it is urgent to exploit an excellent way to monitor SO 2 derivatives in biological system. Herein, we design a water-soluble ratiometric fluorescent probe to fast detect the level of SO 2 derivatives in living cells in vivo. The probe displays obvious fluorescence signal at long wavelength, which is helpful for imaging of biological system. After respond to SO 2 derivatives, the fluorescence signal at 465 nm increases rapidly due to the Michael addition reaction is triggered, further causing the disruption of large conjugated system . The probe exhibits high selectivity and fast respond to SO 2 derivatives, which can be able to sensitive and real-time monitoring of SO 2 derivatives level in living cells. Moreover, the probe reveals a low detection limit and a great linear relationship to SO 2 derivatives. Based on the negligible cytotoxicity and good biocompatibility of the probe, which is employed to detect exogenous and endogenous SO 2 derivatives in living cells. In addition, it is also served as a potential chemical tool to detect SO 2 derivatives in mice model of sinusitis .
研究领域:
生物化学
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医学诊断
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分子影像学
✓ 已验证
DOI
高影响因子
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