研究目的
To detect incipient gastrointestinal (GI) tract cancers and facilitate targeted biopsies and improve therapeutic intervention by assessing whether SERRS-NPs can enable detection of pre-malignant GI lesions and accumulate sufficiently for imaging using Raman endoscopy.
研究成果
SERRS-NP-based Raman endoscopy enables highly sensitive detection of pre-malignant GI lesions in animal models, with potential for clinical translation to improve early cancer detection and reduce morbidity and mortality.
研究不足
The study is limited to animal models, and translation to humans requires further validation. Intravenous administration leads to accumulation in liver and spleen, necessitating long-term toxicity studies. False positives from gut-associated lymphoid tissue (GALT) were noted in mouse models.
1：Experimental Design and Method Selection:
The study used surface-enhanced resonance Raman scattering nanoparticles (SERRS-NPs) for contrast-enhanced Raman imaging. The methodology involved synthesizing PEGylated SERRS-NPs, characterizing them, and using them in animal models of GI carcinogenesis. Raman imaging was performed with commercial systems, a custom-built mouse endoscope, and a clinical-grade endoscope.
2：Sample Selection and Data Sources:
Animal models included L2-hIL-1β mice for esophageal lesions, Helicobacter felis-infected/MNU-treated GAS-KO mice for gastric lesions, ApcMin/+ mice for intestinal lesions, and ApcPirc/+ rats for colorectal lesions. Samples were selected based on genetic predispositions and treatments to mimic human disease.
3：List of Experimental Equipment and Materials:
Equipment included transmission electron microscope (JEOL 1200-EX II), nanoparticle tracking analyzer (NS500, Malvern), Raman spectroscopy systems (InVia system, MiniRam spectrometer), custom-built mouse Raman endoscope, and clinical Raman/white light endoscope. Materials included gold nanoparticles, IR780 perchlorate dye, silica, PEG, and various chemicals from Sigma Aldrich.
4：Experimental Procedures and Operational Workflow:
SERRS-NPs were synthesized, characterized, and injected intravenously into animals. Raman imaging was performed ex vivo and in vivo using different endoscopes. Tissues were processed for histology and immunohistochemistry to validate findings.
5：Data Analysis Methods:
Raman data were analyzed using direct classical least square (DCLS) algorithm in Wire 3.4 software. Sensitivity and positive predictive values were calculated based on histology correlations.
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Transmission Electron Microscope
JEOL 1200-EX II
JEOL
Used for characterizing the size and morphology of SERRS-NPs.
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Nanoparticle Tracking Analyzer
NS500
Malvern
Used to determine hydrodynamic diameter and concentration of SERRS-NPs.
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Optical Fiber
FG550LEC
Thorlabs
Part of the custom-built mouse Raman endoscope for light transmission.
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Raman Spectroscopy System
InVia
Renishaw
Used for Raman imaging of tissues with SERRS-NPs.
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Raman Spectrometer
MiniRam
B&WTek
Used with the custom-built mouse endoscope for spectroscopic detection.
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Spectroscopic Probe
BAC100
B&WTek
Used in the custom-built endoscope for Raman signal collection.
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White Light Endoscope
EPK-1000
Pentax
Used for conventional endoscopic imaging in dual-modality studies.
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Charge-Coupled Device Detector
Used in Raman systems for signal detection.
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