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基于氧化石墨烯/金纳米棒的表面增强拉曼散色技术检测循环肿瘤细胞
朱欢欢1,李晓峰2,朱晋峰2,黄鑫1,何奇3,陈炳地1,曹玮3*
0
(1. 同济大学医学院生物医学工程与纳米科学研究院, 上海 200092;
2. 福建医科大学附属泉州市第一医院肿瘤内科, 泉州 362000;
3. 上海交通大学医学院附属国际和平妇幼保健院乳腺科, 上海 200030
*通信作者)
摘要:
目的 开发一种结合表面增强拉曼散色(SERS)光谱与静电吸附的方法用于检测循环肿瘤细胞。方法 氧化石墨烯经过聚苯乙烯磺酸钠(PSS)的非共价修饰后,通过金种子法原位合成氧化石墨烯/金纳米棒(GO/GNR)复合材料,再利用聚-二烯丙基二甲基氯化铵(PDDAC)非共价修饰GO/GNR,使其表面带正电荷。通过电荷靶向作用实现GO/GNR与肿瘤细胞的靶向结合,用SERS技术对GO/GNR-肿瘤细胞复合物进行检测。采集健康志愿者血液标本,将不同密度的肿瘤细胞加入血液标本中制成模拟血样,按上述方法检测模拟血样中的肿瘤细胞。结果 带正电荷的GO/GNR复合材料能够有效地与肿瘤细胞靶向结合,并且能够在50~10 000个细胞的范围内对肿瘤细胞进行拉曼光谱检测,但白细胞对肿瘤细胞的检测有一定的干扰。结论 GO/GNR复合材料可作为SERS探针实现对循环肿瘤细胞的拉曼光谱检测。
关键词:  氧化石墨烯  金纳米棒  循环肿瘤细胞  表面增强拉曼散色  痕量检测
DOI:10.16781/j.0258-879x.2019.06.0643
投稿时间:2018-01-07修订日期:2019-05-22
基金项目:国家自然科学基金面上项目(81772285,31671029),上海市卫生和计划生育委员会优秀青年人才培养计划(2017YQ051),上海市科学技术委员会课题(17411968700,18441900300).
Surface-enhanced Raman scattering technology-based graphene oxide/gold nanorods in detection of circulating tumor cells
ZHU Huan-huan1,LI Xiao-feng2,ZHU Jin-feng2,HUANG Xin1,HE Qi3,CHEN Bing-di1,CAO Wei3*
(1. Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, China;
2. Department of Oncology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362000, Fujian, China;
3. Department of Breast, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
*Corresponding author)
Abstract:
Objective To develop a method combining surface-enhanced Raman scattering (SERS) spectrum and electrostatic adsorption for detecting circulating tumor cells. Methods Graphene oxide was non-covalently functionalized by poly(sodium-p-styrenesulfonate) (PSS), and graphene oxide/gold nanorod (GO/GNR) hybrids were in situ synthesized via gold seeding growth approach. Then, GO/GNR hybrids were non-covalently functionalized by poly dimethyl diallyl ammonium chloride (PDDAC) to make the surface of GO/GNR positively charged. GO/GNR hybrids would target the tumor cells by electrostatic interaction. SERS technology was used to detect the composites of GO/GNR-tumor cells. The blood samples of healthy volunteers were collected, and the tumor cells of different densities were added to the blood samples to make simulated blood samples. The tumor cells in simulated blood samples were detected using the above methods. Results Positively charged GO/GNR hybrids could efficiently target the tumor cells. SERS spectroscopy could detect tumor cells within 50 to 10 000 cells. However, white blood cells might interfere the detection of tumor cells. Conclusion GO/GNR hybrids may serve as SERS probes for detection of circulating tumor cells via Raman spectroscopy.
Key words:  graphene oxide  gold nanorods  circulating tumor cells  surface-enhanced Raman scattering  trace detection