- 标题
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- 实验方案
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Visualizing Nitric Oxide in Mitochondria and Lysosomes of Living Cells with N-Nitrosation of BODIPY-based Fluorescent Probes
摘要： Nitric oxide (NO), a ubiquitous gasotransmitter which plays critical roles in cardiovascular, nervous, and immune systems related diseases, is closely related in the physiological and pathological processes of mitochondria and lysosomes. Thus, monitoring NO in mitochondria or lysosomes is very meaningful for NO related chemical biology. Herein, we rationally designed four NO probes, BDP-NO, Mito-NO-T, Mito-NO and Lyso-NO, based on BODIPY dye substituted at meso position with 5-amino-2-methoxy-phenyl scaffold. These four probes all showed fast fluorescence off-on response toward NO with excellent selectivity and high sensitivity with the detection limit of BDP-NO to reach 5.7 nM. We introduced triphenylphosphonium and morpholine moieties onto BODIPY scaffold respectively to enable organelle-targetability. MTT and flow cytometry assay demonstrated that the probes exhibited low cytotoxicity, which was beneficial to the biological application in living cells. Confocal fluorescence microscopy experiments confirmed excellent mitochondria targeting for Mito-NO and lysosome-targeting with Lyso-NO for the detection of NO in living cells.
关键词： Fluorescent probes,Mitochondria-targeted,Lysosomes-targeted,BODIPY,Nitric oxide
更新于2025-11-21 11:08:12
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A mitochondria-targeted ratiometric fluorescent probe for detection of SO2 derivatives in living cells and in vivo
摘要： A new near-infrared (NIR) ?uorescent probe for colorimetric and ratiometric detection of SO2 derivatives was developed based on conjugated hybrid coumarin-hemicyanine. The probe can detect HSO3?/SO32? in HEPES bu?er (10 mM, pH 7.4, with 10% DMF, v/v) with a large emission shift (259 nm). Importantly, it was successfully used for ?uorescence imaging of endogenous bisul?te in BT-474 cells and zebra?sh.
关键词： Near-infrared ?uorescent probe,SO2 derivatives,Mitochondria-targeted,Ratiometric,Colorimetric
更新于2025-11-19 16:56:35
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Suppression of Light-Induced Oxidative Stress in the Retina by Mitochondria-Targeted Antioxidant
摘要： Light-induced oxidation of lipids and proteins provokes retinal injuries and results in progression of degenerative retinal diseases, such as, for instance, iatrogenic photic maculopathies. Having accumulated over years retinal injuries contribute to development of age-related macular degeneration (AMD). Antioxidant treatment is regarded as a promising approach to protecting the retina from light damage and AMD. Here, we examine oxidative processes induced in rabbit retina by excessive light illumination with or without premedication using mitochondria-targeted antioxidant SkQ1 (10-(6’-plastoquinonyl)decyltriphenyl-phosphonium). The retinal extracts obtained from animals euthanized within 1–7 days post exposure were analyzed for H2O2, malondialdehyde (MDA), total antioxidant activity (AOA), and activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) using colorimetric and luminescence assays. Oxidation of visual arrestin was monitored by immunoblotting. The light exposure induced lipid peroxidation and H2O2 accumulation in the retinal cells. Unexpectedly, it prominently upregulated AOA in retinal extracts although SOD and GPx activities were compromised. These alterations were accompanied by accumulation of disulfide dimers of arrestin revealing oxidative stress in the photoreceptors. Premedication of the eyes with SkQ1 accelerated normalization of H2O2 levels and redox-status of lipids and proteins, contemporarily enhancing AOA and, likely, sustaining normal activity of GPx. Thus, SkQ1 protects the retina from light-induced oxidative stress and could be employed to suppress oxidative damage of proteins and lipids contributing to AMD.
关键词： SkQ1,superoxide dismutase,glutathione peroxidase,disulfide dimerization of proteins,visual arrestin,age-related macular degeneration,mitochondria-targeted antioxidant,antioxidant activity,light-induced retinal damage,oxidative stress
更新于2025-09-23 15:23:52
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Selective Visualization of Live-Cell Mitochondrial Thiophenols and Their Induced Oxidative Stress Process by a Rationally Designed Rhodol-Based Fluorescent Probe
摘要： Mitochondria as cellular powerhouses are the preferential targets affected by thiophenols, an important class of highly toxic environmental pollutants, and are linked to the production of pathogenic reactive oxygen species (ROS) induced by trace thiophenol residues. For real-time and accurate sensing, it is critically important to develop highly sensitive fluorescent probes for the specific detection of mitochondrial thiophenols. Herein, we report the first mitochondria-targeted fluorescent probe (ROAL) to image thiophenols in living cells. The development of ROAL was based on a novel red-emitting rhodol derivative (ROAP). ROAL proved to be highly selective to thiophenols among various analytes including aliphatic thiols, and renders an ultrasensitive off-on fluorescence response to thiophenols with a remarkable detection limit (8.1 nM). The probe efficiently stains mitochondria with a high Pearson’s co-localization coefficient (0.95) using Mito Tracker Green FM as reference, thereby ensuring the specific detection of mitochondrial thiophenols in living HepG2 and HeLa cells. In particular, using this probe we for the first time proved that endogenous reactive oxygen species have the capacity to eliminate thiophenols in living cells, suggesting that thiophenols might induce cellular oxidative stress.
关键词： oxidative stress damage,fluorescent probe,live-cell imaging,thiophenol,mitochondria-targeted
更新于2025-09-23 15:19:57
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A highly selective and sensitive fluorescent probe for simultaneously distinguishing and sequentially detecting H <sub/>2</sub> S and various thiol species in solution and in live cells
摘要： A novel dual-channel fluorescent probe (NCR) based on differences in reactivity among H2S, Cys/Hcy, and GSH was rationally designed for simultaneously distinguishing and sequentially sensing H2S, Cys/Hcy, and GSH using two emission channels, which also demonstrated that NCR can be used for targeting mitochondria in mammalian cells.
关键词： live cells,thiol species,fluorescent probe,mitochondria-targeted,H2S
更新于2025-09-19 17:15:36
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Thulium Laser‐Assisted Versus Conventional Laparoscopic Partial Nephrectomy for the Small Renal Mass
摘要： Mitochondria-targeting cancer therapies have achieved unprecedented advances attributed to their superior ability for improving drug delivery efficiency and producing an enhanced therapeutic effect. Herein, we report a mitochondria-targeting camptothecin (CPT) polyprodrug system (MCPS) covalently decorated with a high-proportioned CPT content, which can realize drug release specifically responsive to a tumor microenvironment. The nonlinear structure of MCPS can form water-soluble unimolecular micelles with high micellar stability and improved drug accumulation in tumoral cells/tissues. Furthermore, a classical mitochondria-targeting agent, triphenylphosphonium bromide, was tethered in this prodrug system, which causes mitochondrial membrane potential depolarization and mediates the transport of CPT into mitochondria. The disulfide bond in MCPS can be cleaved by an intracellular reductant such as glutathione, leading to enhanced destruction of mitochondria DNA and cell apoptosis induced by a high level of reactive oxygen species. The systematic analyses both in vitro and in vivo indicated the excellent tumor inhibition effect and biosafety of MCPS, which is believed to be an advantageous nanoplatform for subcellular organelle-specific chemotherapy of cancer.
关键词： chemotherapy,reduction-activated,mitochondria-targeted,polyprodrug,cancer therapy
更新于2025-09-11 14:15:04