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目的:利用金纳米棒标记的人细胞因子诱导杀伤细胞(CIK)主动靶向体内胃癌细胞的特性,实现胃癌的局部光声成像,观察金纳米棒在胃癌组织中的分布,测量血清中细胞因子浓度变化。方法:取健康志愿者的全血提取外周血单个核细胞,在多种细胞因子的诱导下扩增出CIK细胞;采用种子合成法制备金纳米棒并对其表面进行二氧化硅修饰与表征;利用胃癌细胞系MGC803细胞建立裸鼠胃癌皮下瘤模型;制备金纳米棒标记的CIK细胞,尾静脉注射进入荷胃癌的裸鼠模型,注射后不同时间点,进行光声成像观察金纳米棒标记的CIK细胞在肿瘤部位的分布;注射后3 d,收集裸鼠血清,测量IL-2、IL-17、γ-IFN的浓度,评判免疫治疗效果。结果:CIK细胞成功制备;制备的金纳米棒长为60 nm,宽为8 nm,二氧化硅厚度为20 nm;制备的金纳米棒被人CIK细胞内吞;金纳米棒标记的人CIK细胞能够主动靶向体内胃癌组织,在胃癌组织中大量聚集,呈现出增强的光声成像信号;细胞因子IL-2、IL-17与γ-IFN的浓度显著升高(P<0.05)。结论:金纳米棒标记的CIK细胞能够主动靶向体内胃癌组织,高效聚集并呈现出增强的光声成像信号,同时升高血液中细胞因子水平,增强免疫治疗功能。
OBJECTIVE: To use gold nanorods labeled human cytokine-induced killer cells (CIKs) to actively target the characteristics of gastric cancer cells in vivo, to achieve local photoacoustic imaging of gastric cancer, to observe the distribution of gold nanorods in gastric cancer tissues, and to measure the levels of cytokines Concentration changes. Methods: Peripheral blood mononuclear cells (PBMCs) were extracted from whole blood of healthy volunteers and CIK cells were expanded under the induction of various cytokines. Gold nanorods were prepared by seed synthesis and their surface was modified and characterized by silica. The gastric cancer subcutaneous tumor model was established by using the gastric cancer cell line MGC803. The gold nanometer rod-labeled CIK cells were prepared and injected into the gastric cancer-bearing nude mice model by tail vein injection. At different time points after injection, CIK cells in the tumor site distribution; 3 d after injection, nude mice sera were collected, the concentration of IL-2, IL-17, γ-IFN was measured to evaluate the effect of immunotherapy. Results: The CIK cells were successfully prepared. The prepared gold nanorods were 60 nm in length, 8 nm in width and 20 nm in thickness. The prepared gold nanorods were endocytosed by human CIK cells and human nanobarbuled human CIK cells It can actively target the gastric cancer tissue in vivo and accumulate in the gastric cancer tissue in a large amount, showing enhanced photoacoustic imaging signals. The concentrations of cytokines IL-2, IL-17 and γ-IFN were significantly increased (P <0.05). CONCLUSION: CIK cells labeled with gold nanorods can actively target gastric cancer tissues in vivo, accumulate efficiently and exhibit enhanced photoacoustic imaging signals, meanwhile, increase cytokine levels in blood and enhance immunotherapy functions.