研究目的
To develop multifunctional theranostic nanoplatforms that respond to near-infrared light for on-demand drug release and multimodal imaging-guided combination cancer therapy.
研究成果
The ID@TSL-Gd NPs successfully achieved NIR-triggered drug release, multimodal imaging (FL/PAI/MRI), and effective combination cancer therapy (Chemo/PTT/PDT) with high tumor targeting and minimal side effects, providing a promising platform for cancer theranostics.
研究不足
The study may have limitations in terms of scalability for clinical translation, potential immunogenicity of the NPs, long-term toxicity not fully assessed beyond 14 days, and the need for further optimization of drug loading and release kinetics. The use of animal models may not fully replicate human physiology.
1:Experimental Design and Method Selection:
The study involved synthesizing ID@TSL-Gd NPs using a nanoprecipitation method derived from previous reports, incorporating a eutectic mixture of lauric acid and stearic acid as a phase change material core, co-encapsulating ICG and DOX, and modifying with folate and gadolinium chelates for targeting and MRI enhancement. Methods included UV-vis spectroscopy, TEM, DLS, in vitro drug release studies, photothermal and photodynamic effect measurements, cellular uptake assays, cytotoxicity analysis, and in vivo imaging and therapy in HeLa tumor-bearing mice.
2:Sample Selection and Data Sources:
HeLa cells and NIH-3T3 cells were used for in vitro studies, and female nude mice with subcutaneous HeLa tumors were used for in vivo experiments. Data were sourced from laboratory experiments and measurements using various instruments.
3:List of Experimental Equipment and Materials:
Equipment included UV3600 UV/vis/NIR spectrophotometer (Shimadzu), HT7700 TEM, particle size analyzer (Brookhaven Instruments), ALV/CSG-3 laser light scattering spectrometers for DLS, Zeiss LSM 780 confocal microscope, IVIS Lumina K in vivo fluorescence imaging system (PerkinElmer), Endra Nexus 128 photoacoustic computerized tomography scanner,
4:0 T clinical MR scanner (GE Healthcare), FLIR E50 infrared thermal imaging camera, and flow cytometry (Flowsight, Merck Millipore). Materials included Diethylenetriaminepentaacetic Dianhydride (DTPA), stearylamine (SA), N, N-dimethylformamide (DMF), Gadolinium (III) chloride hexahydrate (Aladdin), DSPE-PEG-FA (MW:
2000), lecithin (Shanghai Yare Biotech), lauric acid, stearic acid, Indocyanine Green (ICG), Doxorubicin (DOX), Dimethyl sulfoxide (DMSO) (Sigma-Aldrich), and various biochemical reagents.
5:Experimental Procedures and Operational Workflow:
Synthesis of Gd-DTPA-SA and ID@TSL-Gd NPs, characterization of NPs (size, morphology, absorption spectra), in vitro drug release under NIR irradiation, measurement of photothermal and photodynamic effects, cellular uptake and targeting studies, NIR-triggered drug release in cells, ROS detection, cytotoxicity assays (MTT, flow cytometry), in vivo imaging (FL, PAI, MRI), and in vivo combination therapy with monitoring of tumor volume and body weight.
6:Data Analysis Methods:
Data were analyzed using standard curves for drug quantification, statistical analysis (e.g., p-values for significance), and software tools for imaging analysis (e.g., for FL, PAI, MRI signals).
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UV/vis/NIR spectrophotometer
UV3600
Shimadzu
Examining absorption spectra of samples
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Confocal microscope
LSM 780
Zeiss
Observing fluorescence in cells
ZEISS LSM 990 Spectral Multiplex
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In vivo fluorescence imaging system
IVIS Lumina K
PerkinElmer
Capturing in vivo fluorescence images
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Infrared thermal imaging camera
FLIR E50
FLIR
Monitoring temperature changes
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Transmission electron microscope
HT7700
Obtaining morphology and size of nanoparticles
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Particle size analyzer
Brookhaven Instruments
Measuring size distribution of nanoparticles
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Dynamic light scattering detector
ALV/CSG-3
Measuring particle size distribution and polydispersity index
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Photoacoustic computerized tomography scanner
Endra Nexus 128
Performing photoacoustic imaging
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Magnetic resonance scanner
3.0 T
GE Healthcare
Performing magnetic resonance imaging
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Flow cytometry
Flowsight
Merck Millipore
Analyzing cell apoptosis
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