Application of the near infrared-Ⅱ fluorescent targeting probe in vivo imaging of liver cancer
Objective To explore the feasibility and imaging performance of galactose-targeted nanoprobe Gal-OH-BDP(GOB)for orthotopic hepatocelluar carcinoma in near infrared-Ⅱ(NIR-Ⅱ)fluo-rescence imaging.Methods NIR-Ⅱ fluorescent probe GOB was synthesized,and the orthotopic hepato-cellular carcinoma model of BALB/c nude mice(Hangzhou Ziyuan Experimental Animal Technology Co.,Ltd.)was established using human HepG2 hepatoma cells(Guangzhou Huatuo Biotechnology Co.,Ltd.).A total of 12 nude mice were randomly assigned into two groups using the simple random sampling,each consisting of 6 mice.Mice injected intratumorally with GOB for NIR-Ⅱ imaging were assigned into NIR-ⅡGOB group(6 cases),while those receiving intravenous injections of indocyanine green(ICG)and subse-quently imaged in both near infrared-Ⅰ(NIR-Ⅰ)and NIR-Ⅱ window were assigned into NIR-Ⅰ ICG group(6 cases)and NIR-Ⅱ ICG group(6 cases),respectively.The imaging experiment in vivo was car-ried out with NIR-Ⅰ/Ⅱ optical instruments.The fluorescence images were processed by Image J software,and the tumor-to-normal tissue ratio(TNR)and resolution of images of the tumor edge were quantitatively calculated.The pathology was verified by paraffin section and hematoxylin-eosin staining.The data were analyzed by t test and analysis of variance.Results Pathological validation confirmed the targeted accu-mulation of GOB in liver cancer tissues post-intratumoral injection.TNR in NIR-Ⅱ GOB group was higher than that in NIR-Ⅱ ICG group and NIR-Ⅰ ICG group(5.61±0.98 vs.3.35±0.63 vs.2.01±0.54,F=29.022,P＜0.05).The subgroup analysis of three indexes of TNR(tumor region fluorescence,normal liver tissue background fluorescence and environmental background fluorescence)showed that in terms of tumor region fluorescence,the NIR-Ⅱ GOB group showed higher levels than the NIR-Ⅱ ICG group(228.04±5.60 vs.207.62±14.86,t=3.149,P＜0.05).In the normal liver tissue background fluores-cence,the NIR-Ⅱ GOB group had lower fluorescence than the NIR-Ⅱ ICG group(43.22±8.68 vs.63.47±8.88,t=-3.992,P＜0.05).By calculating the gray value change rate across the tumor edge pixels to quantify the resolution of images of the tumor edge,NIR-Ⅱ GOB group demonstrated higher tumor edge resolution than both the NIR-Ⅱ ICG and NIR-Ⅰ ICG groups(170.01±30.92 vs.98.96±23.99 vs.36.82±10.19,F=48.882,P＜0.05).Conclusion This study achieved superior in orthotopic hepa-tocelluar carcinoma fluorescence imaging in the NIR-Ⅱ window through intratumoral injection of the Gal-OH-BDP nanoprobe,outperforming traditional ICG-mediated imaging.
Near infrared-ⅡFluorescence imagingOrthotopic liver tumorsGalactose-targeting
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