研究目的
To develop an interventional photothermal-brachytherapy (IPT-BT) synergistic therapy using biodegradable honeycomb-like gold nanoparticles (HGNs) for the treatment of deep tumors, specifically pancreatic cancer, by overcoming limitations of traditional photothermal-radiotherapy such as poor tissue penetration and high radiation side effects.
研究成果
The IPT-BT synergistic therapy using biodegradable HGNs effectively treats deep pancreatic tumors with a high inhibition rate (96.6%), reduces hypoxia-related resistance, enhances DNA damage, and shows good biocompatibility with minimal side effects. This approach holds promise for clinical translation in treating deep malignant tumors beyond pancreatic cancer.
研究不足
The study is focused on pancreatic cancer models in mice, which may not fully translate to human patients. The interventional procedure requires specialized equipment and expertise, potentially limiting widespread clinical application. Long-term toxicity and biodegradation effects in humans are not fully established. The strategy's efficacy for other deep tumors needs further validation.
1:Experimental Design and Method Selection:
The study designed an IPT-BT synergistic therapy combining interventional photothermal therapy (IPTT) and brachytherapy (BT) using HGNs. HGNs were synthesized via an in situ reduction method to serve as both photothermal agents and radiosensitizers. Theoretical models included the use of localized surface plasmon resonance (LSPR) for photothermal conversion and X-ray attenuation for radiosensitization.
2:Sample Selection and Data Sources:
Human pancreatic adenocarcinoma cell lines (SW1990 and PANC-1) were used for in vitro experiments. BALB/c nude mice with orthotopic SW1990 pancreatic tumors served as the in vivo model. Data were sourced from cell culture, animal studies, and various imaging and analytical techniques.
3:List of Experimental Equipment and Materials:
Equipment included scanning electron microscope (SEM), dynamic light scattering (DLS) instrument (Zetasizer Nano-ZS), X-ray photoelectron spectroscopy (XPS) system (Axis HSi), UV-visible spectrophotometer (SHIMADZU 2600), flow cytometer, infrared thermal imager, photoacoustic imaging system (MSOT inVision 128), bioluminescence imaging system (IVIS Spectrum Imaging System), and ultrasound imaging. Materials included liposomes (DOPE, DPPC, DSPE-PEG2000), gold precursors (HAuCl4·3H2O), reducing agents (hydroxylamine hydrochloride), cell culture reagents, and radioactive seeds (iodine-125).
4:5). Experimental Procedures and Operational Workflow:
4. Experimental Procedures and Operational Workflow: HGNs were synthesized and characterized. In vitro studies involved cell viability assays (MTT), clonogenic survival assays, apoptosis analysis (flow cytometry with Annexin V-PE/7-AAD), and DNA damage assessment (γ-H2AX staining). In vivo studies included biodistribution analysis using fluorescence and ICP-MS, photoacoustic imaging, thermal imaging during laser irradiation, and therapeutic efficacy evaluation in tumor-bearing mice with groups receiving different treatments (control, BT alone, HGNs + BT, HGNs + IPTT, HGNs + IPT-BT). Treatments involved intravenous injection of HGNs, implantation of 125I seeds under ultrasound guidance, and laser irradiation via interventional fiber.
5:Data Analysis Methods:
Data were analyzed using statistical methods (t-test) with significance set at P < 0.01. Software included Image J for immunohistochemical analysis and instruments' built-in software for imaging and spectroscopy data.
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Zetasizer Nano-ZS
Nano-ZS
Malvern Instruments
Measuring dynamic light scattering for size distribution of nanoparticles.
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Axis HSi X-ray photoelectron spectroscopy system
Axis HSi
Kratos Ltd.
Analyzing surface chemistry of nanoparticles.
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2600 UV-Visible Spectrophotometer
2600
SHIMADZU
Obtaining UV-vis absorption spectra.
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IVIS Spectrum Imaging System
IVIS Spectrum
PerkinElmer
Performing bioluminescence imaging.
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HT-7700 electron microscope
HT-7700
Characterizing morphology of nanoparticles.
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APOLLO XLT2 transmission electron microscope
APOLLO XLT2
Performing element mapping and energy-dispersive X-ray spectroscopy.
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S-4700 scanning electron microscope
S-4700
Characterizing size and morphology of nanoparticles.
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MSOT inVision 128
inVision 128
iThera medical
Capturing photoacoustic signals for in vivo imaging.
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NIR laser fiber
0.8 mm
Banglei Optoelectronic Technology Co., Ltd
Delivering NIR laser for photothermal therapy.
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Hollow percutaneous transhepatic cholangiography needle
Zhuhai Hokai Biomedical Electronics Co., Ltd.
Penetrating into deep abdominal cavity for interventional procedures.
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Iodine-125 seed
125I
Implanting as a radioactive source for brachytherapy.
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