新型塔斯品碱荧光探针与肿瘤细胞示踪成像分析研究

Fluorescent tracer imaging analysis is widely used in an effective visualization of live cell analysis. At this stage, most of the fluorescent probes used in imaging analysis of tumor cells can only be used in research and clinical marker test as a detection tool. In the previous study, taspine was screened for the first time as an active ingredient from Radix et Rhizoma Leonticis (Hong Mao Qi in Chinese, HMQ) using cell membrane chromatography (CMC). In this project, based on the techniques of computer-aided drug design and cell membrane chromatography model screening, we use taspine diphenyl derivative as the identified group, design and synthesize the new fluorescent probes, which can recognize the tumor cells specifically. Subsequently, the fluorescence and the activity of tumor cell recognition of the new probes are test. The effective images are also captured. Based on the direct monitoring of the number, morphology and structure of the tumor cells, we can establish a new fluorescent tracer analysis method for tumor cells. The success of this study can provide a certain theoretical basis for the initial establishment of a more intuitive, accurate technology for the tumor diagnosis. The results can be used to evaluate the mechanism of the action and the efficacy of anti-tumor drugs. We further hope that this research can be used in the screening of anti-tumor drug candidates, thereby contributing to the progress of anti-tumor drugs.

荧光示踪成像分析是目前广泛应用于活细胞分析的一种有效的可视化分析技术。现阶段，大多数应用于肿瘤细胞成像分析的荧光探针仅可作为一种检测工具应用于科研及临床的标记检验中。本项目通过筛选秦巴山区特有的药用植物红毛七，将其活性成分塔斯品碱的联苯衍生物作为探针的识别基团，综合利用计算机辅助药物设计，结合细胞膜色谱模型筛选技术，通过引入荧光发色基团，设计、合成对肿瘤细胞有特异性识别功能的新型塔斯品碱荧光探针；通过对其荧光特性及肿瘤细胞识别活性的考察，实现对肿瘤细胞的成像；通过对肿瘤细胞数目、形态、结构及生命现象的直接监测，建立肿瘤细胞荧光示踪分析的新方法。该项目的成功研究将为初步建立一种更为直观、准确的肿瘤诊断新技术提供一定理论依据；同时可对抗肿瘤药物的作用机制和作用效果进行研究、评价，进一步应用于抗肿瘤候选药物的筛选工作中，从而促进抗肿瘤药物的研究。

荧光示踪成像分析是目前广泛应用于活细胞分析的一种有效的可视化分析技术。现阶段，大多数应用于活细胞成像分析的荧光探针仅可作为一种检测工具应用于科研及临床的标记检验中，自身并不具备生物活性。本项目通过筛选药用植物红毛七及白芷，分别将其中的活性成分塔斯品碱的联苯衍生物及欧前胡素作为探针的识别基团，综合利用计算机辅助药物设计，结合细胞膜色谱模型筛选技术，通过引入不同的荧光发色基团，设计、合成对肿瘤细胞、血管平滑肌细胞等活细胞有特异性识别功能的新型荧光探针。通过对其荧光特性及活细胞识别活性的考察，实现对活细胞的成像；通过对活细胞数目、形态、结构及生命现象的直接监测，建立活细胞荧光示踪分析的新方法。该项目的成功研究将为初步建立一种更为直观、准确的细胞病理诊断新技术提供一定理论依据；同时可对相应的抗肿瘤药物、血管药物的作用机制和作用效果进行研究、评价，进一步应用于相应的抗肿瘤药物、血管药物的筛选工作中，从而促进抗相关药物的研究。

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