生物素靶向显影探针Biotin-S-S-Rhodol对乳腺癌细胞的靶向显影作用  

Targeted imaging ability of a biotinylated imaging probe Biotin-S-S-Rhodol for breast cancer cells in vitro

作　　者：吴碧娟[1,2] 周杏子[2] 孙婧雯[2] 谭翠雯 吴新荣[1,2] 

机构地区：[1]南方医科大学研究生院,广东广州510515 [2]广州军区广州总医院药学部,广东广州510010

出　　处：《南方医科大学学报》2017年第1期124-129,共6页Journal of Southern Medical University

基　　金：广东省科技计划项目(2011A080300004);广州市科技计划项目(201509010012)

摘　　要：目的对新型生物素靶向显影探针(Biotin-S-S-Rhodol,3a)的靶向显影性能进行分析。方法采用紫外吸收光谱和荧光光谱分析谷胱甘肽(GSH)处理后3a的光谱特性;采用不同浓度GSH处理3a,荧光光谱分析3a对GSH的敏感性;采用流式细胞术和荧光倒置显微镜观察生物素预处理前后MCF-7细胞、MDA-MB-231细胞和Hs 578Bst细胞对3a的摄取率和靶向显影性能;四甲基偶氮唑盐比色法(MTT)初步分析3a对MCF-7细胞、MDA-MB-231细胞和Hs 578Bst细胞的毒性。结果 3a的最强吸收峰在510 nm处,在544 nm处荧光发射信号最强;荧光光谱结果显示随着GSH浓度(0~6 mmol/L)处理浓度提高,544 nm波长处的荧光强度升高;MDA-MB-231、MCF-7细胞对3a的摄取率明显高于Hs 578Bst细胞;3a能实现乳腺癌细胞专一性成像,成像清晰;2~20μmol/L 3a对人正常乳腺细胞无明显毒性,可在一定程度上抑制MCF-7细胞和MDA-MB-231细胞存活。结论 3a能通过生物素介导专一靶向乳腺癌细胞,成像清晰,对正常乳腺细胞毒性极低,有一定的抑制乳腺癌细胞存活作用。Objective To investigate performance of a biotinylated imaging probe 3a for targeted imaging of breast cancer cells. Methods Ultraviolet absorption spectrum and fluorescence spectrum were employed to analyze the spectral characteristics of 3a. The fluorescence spectrums of 3a treated with different concentrations of glutathione （GSH） were obtained to determine the sensibility of 3a to GSH. Flow cytometry was used to determine the cellular uptake of 3a by MCF-7 cells, MDA-MB-231 cells and Hs 578Bst cells in the presence or absence of biotin, and the imaging performance of 3a in the 3 cell lines was assessed under an inverted fluorescent microscope. The toxicity of 3a to the cells was evaluated using MTT method. Results 3a showed the strongest absorption peak at 510 nm, and its fluorescence emission signal was the strongest at 544 nm. As the concentration of GSH increased （0-6 mmol/L）, 3a exhibited an increasing fluorescence signal at 544 nm. The cellular uptake of 3a was markedly higher in MDA-MB-231 cells and MCF-7 cells than in Hs 578Bst cells. The imaging studies showed that 3a had a good breast cancer cell-targeting property and produced clear images under fluorescent microscope. MTT assay demonstrated no obvious toxicity of 3a in Hs 578Bst cells even at the concentration of 20 μmol/L, but MCF-7 cells and MDA-MB-231 cells exposed to 2-20μmol/L 3a showed a lowered cell viability. Conclusion 3a is capable of targeted imaging of breast cancer cells mediated by biotin. 3a at the concentration of 2-20 μmol/L has minimal cytotoxicity to normal breast cells but can lower the viability of breast cancer cells.

关 键 词：Biotin-S-S-Rhodol 生物素 罗丹明 二硫键 靶向显影 乳腺癌 

分 类 号：R737.9[医药卫生—肿瘤]