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Biomimetic Metal-Organic Framework Nanoparticles for Cooperatively Combination of Antiangiogenesis and Photodynamic Therapy for Enhanced Efficacy
摘要： Photodynamic therapy (PDT) is a promising anticancer treatment and is clinically approved for different types of tumors. However, current PDT suffers several obstacles, including its neutralization by excess glutathione (GSH) in the tumor tissue and its strongly proangiogenic tumor response. In this work, a biomimic, multifunctional nanoparticle-based PDT agent, combining a tumor-targeted photosensitizer with GSH scavenging and antiangiogenesis therapy, is developed. A porphyrinic Zr–metal–organic framework nanoparticle is used simultaneously as the photosensitizer and the delivery vehicle of vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor apatinib. The core nanoparticles are wrapped in MnO2 to consume the intratumoral GSH and then decorated with a tumor cell membrane camouflage. After intravenous administration, the nanoparticles selectively accumulate in tumor through homotypic targeting mediated by the biomimic decoration, and the combination of enhanced PDT and antiangiogenic drug significantly improves their tumor inhibition efficiency. This study provides an integrated solution for mechanism-based enhancement of PDT and demonstrates the encouraging potential for multifunctional nanosystem applicable for tumor therapy.
关键词： glutathione metabolism,photodynamic therapy,MOF,angiogenesis inhibition,biomimetic nanoparticle
更新于2025-11-21 11:08:12
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Detection of Tetracycline in Water Using Glutathione-protected Fluorescent Gold Nanoclusters
摘要： Tetracycline (Tc), a widely used antibiotic, is one of the major pollutants in water. Herein, glutathione (GSH)-protected Au nanoclusters (GSH-AuNCs) were prepared to detect Tc. The fluorescence quenching ratio of GSH-AuNCs shows an excellent linear response against tetracycline in the concentration range of 50 μg/L – 50 mg/L with the detection limit of 5.31 μg/L. For the test paper prepared by GSH-AuNCs, 1 mg/L Tc caused a significant difference that could be recognized by the naked eye. The method exhibited good selectivity and excellent recovery when applied to a tap water sample. The method has the potential for Tc detection in real samples.
关键词： tetracycline detection,Au nanocluster,glutathione,recovery experiment,quenching ratio
更新于2025-11-19 16:56:35
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Kidney toxicity and response of selenium containing protein-glutathione peroxidase (Gpx3) to CdTe QDs on different levels
摘要： The toxic mechanism of cadmium-quantum dot (Cd-QDs) to organisms is still debating. In this paper, it was found that Cd-QDs could induce adverse effects to kidney by entering into cells in a time and dose manner and disturbing the redox balance in vivo. As a selenium containing protein, glutathione peroxidase3 (Gpx3) plays a crucial role in maintaining the balance of redox system. The decrease of Gpx3 activity might be related to the imbalance of redox system. Similar to the animal results, it was demonstrated that Gpx3 activity is also inhibited by Cd-QDs in vitro. To investigate the underlying mechanism of Cd-QDs on conformational and functional changes of Gpx3, systematical measurements including calorimetric, multi-spectroscopic studies and molecular model studies were carried out on molecular level. Results showed that Cd-QDs binds to Gpx3 via Van der Waals' force and hydrogen bonds, resulting in structural changes with increasing contents of α-helix. By interacting with Glu136 in the cavity of Gpx3 as well as Phe132, Pro130 and Van129 surrounded, Cd-QDs changes the micro-environment of fluorophore and further reduce the activity of Gpx3.
关键词： glutathione peroxidase3,redox balance,molecular mechanism,kidney toxicity,Cd-QDs
更新于2025-11-19 16:46:39
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Free-label dual-signal responsive optical sensor by combining resonance Rayleigh scattering and colorimetry for sensitive detection of glutathione based on ultrathin MnO2 nanoflakes
摘要： Glutathione (GSH) plays a critical role in the living system and its abnormalities are closely associated with numerous clinical diseases. Thus, monitoring and detecting the content of GSH in the living system is still of great importance. Herein, a novel dual-signal responsive optical sensor is developed by using resonance Rayleigh scattering (RRS) and colorimetry for sensitive detection of GSH. In this sensor, MnO2 nanoflakes are used as both GSH recognizer and signal transducer of RRS and colorimetry. The solution of MnO2 nanoflakes shows strong RRS and absorption signals because MnO2 nanoflakes possess a large surface area and high molar extinction coefficient. However, MnO2 can be reduced to Mn2+ and MnO2 nanoflakes can be etched to small nanoparticles by GSH, causing both the RRS and absorption signals to decrease. Based on the change of RRS signal and absorbance of MnO2 nanoflakes, a novel dual-signal responsive optical sensor is successfully constructed to detect the content of GSH. The as-developed optical sensor toward GSH presents a favorable sensitivity with a detection limit of 0.033 and 0.67 μM for RRS and colorimetry, respectively. Furthermore, the as-developed approach is straightforward, quickly responsive, free-label, and cost-effective. More significantly, this method combines the advantages of RRS and colorimetry for the detection of GSH. Beyond this, the proposed RRS method has also been successfully utilized to detect the content of GSH in glutathione injection samples.
关键词： Glutathione,Resonance Rayleigh scattering,MnO2 nanoflakes,Colorimetry,Dual-signal
更新于2025-11-14 17:04:02
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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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Structure-based design and application of an engineered glutathione transferase for the development of an optical biosensor for pesticides determination
摘要： In the present work, a structure-based design approach was used for the generation of a novel variant of synthetic glutathione transferase (PvGmGSTU) with higher sensitivity towards pesticides. Molecular modelling studies revealed Phe117 as a key residue that contributes to the formation of the hydrophobic binding site (H-site) and modulates the affinity of the enzyme towards xenobiotic compounds. Site-saturation mutagenesis of position Phe117 created a library of PvGmGSTU variants with altered kinetic and binding properties. Screening of the library against twenty-five different pesticides, showed that the mutant enzyme Phe117Ile displays 3-fold higher catalytic efficiency and exhibits increased affinity towards α-endosulfan, compared to the wild-type enzyme. Based on these catalytic features the mutant enzyme Phe117Ile was explored for the development of an optical biosensor for α-endosulfan. The enzyme was entrapped in alkosixylane sol-gel system in the presence of two pH indicators (bromocresol purple and phenol red). The sensing signal was based on the inhibition of the sol-gel entrapped GST, with subsequent decrease of released [H+] by the catalytic reaction, measured by sol–gel entrapped indicators. The assay response at 562 nm was linear in the range pH = 4–7. Linear calibration curves were obtained for α-endosulfan in the range of 0–30 μM. The reproducibility of the assay response, expressed by relative standard deviation, was in the order of 4.1% (N = 28). The method was successfully applied to the determination of α-endosulfan in real water samples without sample preparation steps.
关键词： Glutathione transferase,Biosensor,α-Endosulfan,Pesticides determination,Protein engineering
更新于2025-09-23 15:23:52
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One pot green synthesis of C-dots from groundnuts and its application as Cr(VI) sensor and in vitro bioimaging agent
摘要： The emergence of ?uorescent carbon dots (C-dots) has received special attention due to their distinct characteristics which are advantageous for optical sensing and bioimaging applications. Cr(VI) is considered a hazardous environmental pollutant hence requires a simple and e?ective method for its detection and recovery. Herein, we have synthesized both C-dots and N-doped C-dots from ground nuts employing a cost-e?ective and green hydrothermal method. N-C-dots exhibits a remarkably enhanced quantum yield (17.6%) as compared to undoped C-dots (7.8%). In addition,the N-C-dots showed amazing selectivity towards Cr(VI) in the metal sensing application. Cr (VI) induced quenching of ?uorescence was recovered using Humic acid as well as Glutathione thus exhibiting an o?-on type sensing mechanism. The limit of detection (LOD) for Cr(VI) using N-C-dots was found to be 0.1 mg/L. C-dots possess comparatively low cytotoxicity than N-C-dots at higher concentration thereby making them an e?cient candidate for bioimaging of MCF-7 cells.
关键词： Bioimaging,Carbon dots(C-dots),Cr(VI) sensing,Groundnut,Glutathione,Humic acid
更新于2025-09-23 15:23:52
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Biodegradability of Disulfide-Organosilica Nanoparticles Evaluated by Soft X-ray Photoelectron Spectroscopy: Cancer Therapy Implications
摘要： Two kinds of organosilica nanoparticles (NPs) that were fabricated from thiol-containing precursors, (3-mercaptopropyl)trimethoxysilane and (3-mercaptopropyl)methyldimethoxysilane (MPDMS), are potential delivery vehicles of anticancer drugs. MPMS can form three siloxane bonds, but MPDMS forms two siloxane bonds as the maximum limit. Hence, disulfide bonds can be involved in the three-dimensional morphology of MPDMS NPs. In addition, NPs containing disulfide bonds are potentially degraded by a reduced form of glutathione (GSH). To examine reactions between the organosilica NPs and GSH, the NPs were incubated in 10 mM GSH aqueous solution at 37 °C for 7 d and the products were analyzed using field-emission scanning electron microscopy (FE-SEM), Raman spectroscopy, and soft X-ray photoelectron spectroscopy (XPS). The Raman spectra showed the presence of disulfide bonds in the MPDMS NPs and the absence of disulfide bonds in MPMS NPs. The results of XPS measurements suggested that the disulfide bonds in the outer layer of MPDMS NPs were reduced to thiol groups. FE-SEM observations of MPDMS NPs detected changes in NP morphology after the GSH incubation. These results support the idea that MPDMS NPs contain disulfide bonds and are degradable by GSH. Therefore, MPDMS NPs possess a biodegradable feature that is advantageous for clinical translation, that is, nanomedicine.
关键词： (3-mercaptopropyl)methyldimethoxysilane,nanoparticles,(3-mercaptopropyl)trimethoxysilane,biodegradability,glutathione,X-ray photoelectron spectroscopy,Raman spectroscopy
更新于2025-09-23 15:22:29
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Switchable Photoacoustic Imaging of Glutathione Using MnO2 Nanotubes for Cancer Diagnosis
摘要： Glutathione is overexpressed in tumor cells and regulates cancer growth, metastasis and drug resistance. Therefore, detecting glutathione levels may greatly facilitate cancer diagnosis and treatment response monitoring. Photoacoustic (PA) imaging is a noninvasive modality for high-sensitivity, high-resolution, deep-tissue optical imaging. Switchable PA probes that offer signal on/off responses to tumor targets would further improve the detection sensitivity and signal-to-noise ratio of PA imaging. Here we explore the use of MnO2 nanotubes as a switchable and biodegradable PA probe for dynamic imaging of glutathione in cancer. Glutathione reduces black MnO2 nanotubes into colorless Mn2+ ions, leading to decreased and “signal off” PA amplitude. In phantoms, we observed a linear response of reduced PA signals of MnO2 nanotubes to increased glutathione concentrations. Using melanoma as the disease model, we demonstrated that MnO2 nanotubes-based PA imaging of glutathione successfully distinguished B16F10 melanoma cells from BEAS-2b normal cells and discriminated B16F10 tumors from healthy skin tissues. Our results showed that MnO2 nanotubes are a potent switchable and biodegradable PA probe for glutathione imaging in cancer diagnosis.
关键词： photoacoustic imaging,nanotubes,cancer,glutathione,melanoma,switchable contrast reagent,MnO2
更新于2025-09-23 15:21:21
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A Ratiometric Fluorescence Probe for Cisplatin: Investigating Intracellular Reduction of Platinum(IV) Prodrug Complexes
摘要： Pt(IV) prodrug strategy has emerged as an excellent alternative to tackle the problems associated with conventional Pt(II) drug therapy. However, there is a lack of tools to study how this new class of Pt(IV) drugs are processed at the cellular level. Herein, we report the first ratiometric fluorescence probe designed for detecting cisplatin, applied to investigate Pt(IV) anticancer complexes in biological systems. The probe was able to distinguish between cisplatin and its Pt(IV) derivatives, allowing us to probe the intracellular reduction of Pt(IV) prodrug complexes. The correlation between the amount of active Pt(II) species available after intracellular reduction of Pt(IV) complexes to their cytotoxicity and the role glutathione plays in their reduction were investigated.
关键词： Fluorescence probes,Ratiometric,Glutathione,Platinum prodrugs,Anticancer
更新于2025-09-23 15:21:21