荧光-磁共振双功能纳米探针标记9L胶质瘤细胞  

Specific targeting of 9L glioma cells with bifunctional optical and MRI nano-probe

作　　者：孟祥喜[1] 万家齐[2] 张文凯 景猛[1] 宋大勇[4] 赵世光[1] 梁洪生[1] 张毅[1] 蔡伟[2] 刘恩重[1] 

机构地区：[1]哈尔滨医科大学附属第一医院神经外科,黑龙江哈尔滨150001 [2]哈尔滨工业大学材料学院,黑龙江哈尔滨150001 [3]龙华人民医院神经外科,广东深圳518000 [4]哈尔滨医科大学附属第四医院神经外科,黑龙江哈尔滨150001

出　　处：《中国微侵袭神经外科杂志》2007年第8期353-357,共5页Chinese Journal of Minimally Invasive Neurosurgery

基　　金：国家自然科学基金资助项目(30672154;30371458);黑龙江省教育厅科学技术研究项目(11511191)

摘　　要：目的验证9L胶质瘤细胞能否被荧光-磁共振双功能纳米探针特异性、高效性地标记,及标记后能否被光学成像和MRI检出。方法将超顺磁性氧化铁纳米粒子(SPIO)与异硫氰酸荧光素(FITC)和氯霉素(Chlorotoxin)耦联,合成荧光-磁共振双功能纳米探针(SPIOFC)。9L胶质瘤细胞分别与SPIOFC和SPIOF(SPIO-FITC)共培养;同时将神经细胞与SPIOFC共培养,作为胶质瘤细胞的对照。采用普鲁士蓝染色和MRI评价胶质瘤细胞吞噬SPIOFC的情况,并在激光扫描共聚焦显微镜下评价SPIOFC的光学显像能力。结果与SPIOFC共培养的9L胶质瘤细胞的普鲁士蓝染色阳性细胞比例为(99.1±1.0)%明显高于与SPIOF共培养的9L胶质瘤细胞的(4.0±1.8)%。与SPIOFC共培养9L胶质瘤细胞的T2信号强度为(210.8±20.2)明显低于与SPIOF共培养的9L胶质瘤细胞(2 245.8±213.3)。与SPIOFC共培养9L胶质瘤细胞比较,与SPIOFC共培养神经细胞的普鲁士蓝染色阳性细胞比例(0)及T2信号强度(2 533.7±199.2)的差异有统计学意义。在激光扫描共聚焦显微镜下,被胶质瘤细胞吞噬的SPIOFC发出绿色荧光。结论SPIOFC是一个特异性、高效性的9L胶质瘤细胞靶向探针。以SPIOFC为探针,能在MRI和光学显微镜下有效地辨别9L胶质瘤细胞与神经细胞。Objective To determine whether 9L glioma cells can be specifically and efficiently targeted by bifunctional optical and MRI uano-probe, andwhether 9L glioma cells can be detected by MRI and optical imaging. Methods SPIOFC was synthesized by conjugating superparamagnetic iron Oxide nanoparticles （SPIO） with fluorescein isothiocyanate （FITC） and chloromycetin. 9L glioma cells were cultured with SPIOFC and SPIOF （SPIO-FITC） respectively, and neural cells were treated with SPIOFC as control for SPIOFC-targeted glioma cells. The internalization of SPIOFC by glioma cells was assessed by Prussian blue staining and MRI. The optical imaging ability of SPIOFC was evaluated by confocal laser scanning microscopy. Results Percentage of Prussian blue staining positive cell in the 9L cells cultured with SPIOFC （99.1% ± 1.0 %） were significantly more than those in the 9L cells incubated with SPIOF （4.0% ± 1.8 %）. The T2 signal intensity of 9L cultured with SPIOFC （210.8 ± 20.2） were substantially lower than those of 9L cells incubated with SPIOF （2 245.8 ± 213.3）. There were significant differences in percentage of Prussian blue staining positive cell （0） and T2 signal intensity between SPIOFC-treated 9L cells and SPIOFC-treated neural cells （2 533.7 ± 199.2）. SPIOFC internalized by glioma cells exhibited green fluorescence under confocal laser scanning microscope. Conclusion SPIOFC is suitable for specific and efficient targeting 9L glioma cells. MRI and optical imaging in conjunction with SPIOFC can distinguish glioma cells from normal brain tissue cells.

关 键 词：神经胶质瘤 超顺磁性氧化铁 纳米粒子 磁共振成像 显微镜检查 荧光 

分 类 号：R739.4[医药卫生—肿瘤]