研究目的
To develop a facile in-situ growth method to integrate MOF nanoparticle into inorganic nanomaterial and design a fluorescence switch to trigger enhanced photodynamic therapy.
研究成果
The study successfully developed core-shell MOF@MnO2 hybrids with switchable fluorescence and photodynamic activity. The GSH-responsive activation enhanced photodynamic therapy by depleting intracellular GSH and allowing MRI guidance. This approach provides a rational design for multifunctional MOF-inorganic complexes, demonstrating improved tumor eradication and survival in mouse models without significant toxicity.
研究不足
The study may have limitations in the scalability of the in-situ growth method for large-scale production. The specificity and efficiency of GSH-responsive activation in varied biological environments were not fully explored. Potential long-term toxicity or immune responses of the hybrid nanoparticles in vivo were not addressed. The balance between MnO2 and GSH for optimal therapy might be context-dependent and require further optimization.
1:Experimental Design and Method Selection:
The study employed an in-situ growth method to integrate MOF nanoparticles into inorganic nanomaterials (MnO2). This involved synthesizing ZIF-8 and ZrMOF nanoparticles, then growing MnO2 nanodots or nanosheets on their surfaces to form core-satellites or core-shell structures. The fluorescence and photodynamic activity were controlled by MnO2 quenching and GSH reduction. In vitro studies included fluorescence spectroscopy, singlet oxygen generation assays, cytotoxicity tests, and MRI relaxivity measurements. In vivo studies used U87MG tumor-bearing mice to evaluate photodynamic therapy efficacy and MRI-guided therapy.
2:2). This involved synthesizing ZIF-8 and ZrMOF nanoparticles, then growing MnO2 nanodots or nanosheets on their surfaces to form core-satellites or core-shell structures. The fluorescence and photodynamic activity were controlled by MnO2 quenching and GSH reduction. In vitro studies included fluorescence spectroscopy, singlet oxygen generation assays, cytotoxicity tests, and MRI relaxivity measurements. In vivo studies used U87MG tumor-bearing mice to evaluate photodynamic therapy efficacy and MRI-guided therapy. Sample Selection and Data Sources:
2. Sample Selection and Data Sources: Samples included synthesized ZIF-8, ZrMOF, ZIF-FITC@MnO2, and ZrMOF@MnO2 nanoparticles. Data were obtained from laboratory syntheses and characterizations (e.g., TEM, HAADF-STEM, XPS, DLS, UV-vis, fluorescence spectroscopy, LC-MS, ICP). In vivo data came from mice models with U87MG tumors.
3:List of Experimental Equipment and Materials:
Equipment: Transmission electron microscopy (TEM), high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), UV-vis spectrophotometer, fluorescence spectrometer, LC-MS system, ICP instrument, MRI system, confocal microscope (Zeiss LSM 780), plate reader. Materials: Zn(NO3)2, 2-methylimidazole, ZrOCl2, meso-tetra(4-carboxyphenyl)porphyrin (TCPP), benzoic acid, KMnO4, GSH, SOSG, MTT, DAPI, Calcium AM/PI, PEG, DMF, methanol, water, sodium acetate, PBS.
4:Experimental Procedures and Operational Workflow:
Synthesis of ZIF-8 and ZrMOF nanoparticles was performed in methanol or DMF with specific reactants and conditions. In-situ growth of MnO2 involved adding aqueous KMnO4 to nanoparticle solutions with stirring. Fluorescence and singlet oxygen generation were measured with and without GSH treatment. Cytotoxicity was assessed via MTT assay and live/dead staining after laser irradiation. In vivo studies involved intravenous injection of PEGylated nanoparticles into mice, followed by laser irradiation and MRI imaging.
5:Data Analysis Methods:
Data analysis included fluorescence intensity measurements, singlet oxygen quantification using SOSG, cell viability calculation from MTT absorbance, flow cytometry for apoptosis, ICP for Mn release, MRI relaxivity (r1) calculation, and statistical analysis of tumor growth and survival rates.
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Confocal Microscope
LSM 780
Zeiss
Used for fluorescence imaging of cells, such as U87MG cells with MOF nanoparticles.
ZEISS LSM 990 Spectral Multiplex
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Transmission Electron Microscopy
Used for imaging nanoparticle structures, such as ZIF-8, ZIF-FITC@MnO2, and ZrMOF@MnO2.
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High-Angle Annular Dark-Field Scanning Transmission Electron Microscopy
Used for high-resolution imaging and element mapping of ZrMOF@MnO2 nanoparticles.
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X-ray Photoelectron Spectroscopy
Used for surface chemical analysis of ZrMOF@MnO2 nanoparticles.
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Dynamic Light Scattering
Used to measure particle size distribution and colloidal stability of ZrMOF and ZrMOF@MnO2.
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UV-vis Spectrophotometer
Used to measure absorbance spectra of ZrMOF, ZrMOF@MnO2, and GSH-treated samples.
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Fluorescence Spectrometer
Used to measure fluorescence intensity of ZIF-FITC, ZrMOF, and their hybrids with MnO2 and GSH.
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LC-MS System
Used for liquid chromatography-mass spectrometry to analyze GSH and GSSG formation.
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ICP Instrument
Used for inductively coupled plasma analysis to measure Mn release from ZrMOF@MnO2.
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MRI System
Used for magnetic resonance imaging to measure T1 relaxivity and in vivo imaging in mice.
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Plate Reader
Used to measure absorbance in MTT assays for cell viability.
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Laser
Used for irradiation in photodynamic therapy experiments, e.g., 650 nm laser for singlet oxygen generation and cell treatment.
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