研究目的
To develop a multifunctional nanoagent for CT/MRI-guided synergistic radiotherapy and X-ray inducible photodynamic therapy of tumors, aiming to overcome the limitations of traditional photodynamic therapy by using X-rays for deeper tissue penetration and enhanced therapeutic effects.
研究成果
The multifunctional GWOT@MC540 nanoagent successfully enables synergistic RT&X-PDT with dual-modal CT/MRI imaging, showing higher tumor inhibition at lower X-ray doses and low toxicity, demonstrating the potential of nanoscintillators in cancer theranostics and inspiring future designs of efficient nanoagents.
研究不足
The study is a proof-of-concept; further investigations are needed for optimization, such as using clinical megavolt photon beams, reducing required nanoagent concentrations, and exploring X-ray luminescence-mediated imaging. The in vivo studies were conducted on mice, and translation to humans requires additional research.
1：Experimental Design and Method Selection:
The study involved synthesizing Gd2(WO4)3:Tb nanoparticles (GWOT NPs) via a hydrothermal method, coupling them with Merocyanine 540 (MC540) for X-ray inducible photodynamic therapy (X-PDT), and evaluating their dual-modal imaging (CT and MRI) and synergistic therapeutic properties. Theoretical models include energy transfer from X-rays to Tb3+ ions for luminescence and activation of photosensitizers.
2：Sample Selection and Data Sources:
Murine breast cancer cells (4T1) and human bronchial epithelial cells (Beas-2B) were used for in vitro studies. 4T1 tumor-bearing mice were used for in vivo studies. Data were acquired through various characterization techniques and biological assays.
3：List of Experimental Equipment and Materials:
Equipment includes TEM for imaging, XRD for crystallinity analysis, DLS for size measurement, RS-2000 Pro biological system for X-ray irradiation, CCK-8 assay for cytotoxicity, flow cytometry for apoptosis analysis, CT and MRI scanners for imaging. Materials include GWOT NPs, MC540, PEG 600, SOSG indicator, and cell culture reagents.
4：Experimental Procedures and Operational Workflow:
Synthesis of GWOT NPs, PEG coating, MC540 loading, characterization (TEM, XRD, DLS), in vitro studies (1O2 production, cytotoxicity, apoptosis), in vivo studies (imaging, tumor growth inhibition via intratumoral and intravenous injections), data collection under controlled X-ray doses (e.g., 6 Gy).
5：Data Analysis Methods:
Statistical analysis using p-values, linear regression for relaxation rates, comparison of HU values for CT, and survival fractions for therapeutic efficacy.
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Transmission Electron Microscope
Used for imaging the nanoparticles to analyze their size and structure.
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X-ray Diffractometer
Used to analyze the crystalline nature of the nanoparticles.
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Dynamic Light Scattering Analyzer
Used to measure the hydrodynamic diameter of the nanoparticles.
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RS-2000 Pro Biological System
RS-2000 Pro
Used for X-ray irradiation in in vitro and in vivo studies.
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Cell Counting Kit-8
CCK-8
Used for cytotoxicity assessment via cell viability assays.
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Flow Cytometer
Used to characterize apoptosis of cells.
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Computed Tomography Scanner
Used for CT imaging to evaluate contrast properties.
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Magnetic Resonance Imaging Scanner
Used for MRI to evaluate T1-weighted contrast.
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SOSG
Used as an indicator for singlet oxygen production.
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