量子点甲胎蛋白抗体探针毒性及裸鼠体内代谢  

Toxicity of quantum dot-alpha-fetoprotein antibody probes and its metabolism in nude mice

作　　者：陈良冬[1] 何蔓[2] 裴小锋[1] 陈创[1] 庞代文[2] 汤钊猷[3] 李雁[1] 

机构地区：[1]武汉大学中南医院肿瘤科 肿瘤生物学行为湖北省重点实验室,湖北武汉430071 [2]武汉大学化学与分子科学学院,湖北武汉430072 [3]复旦大学肝癌研究所,上海200032

出　　处：《中国药理学与毒理学杂志》2010年第2期122-127,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金资助项目(20675058);国家自然科学基金创新研究群体科学基金(20921062);教育部新世纪优秀人才支持计划(NCET-04-0669);全国优秀博士论文专项资金(200464)~~

摘　　要：目的探讨量子点甲胎蛋白抗体探针的生物相容性及毒性特点。方法将巯基乙酸修饰的水溶性量子点(QD)结合鼠抗人甲胎蛋白(AFP)单克隆抗体(Ab)制备成水溶性QD-AFP-Ab复合物探针,用荧光、紫外光谱分析及透射电镜研究其特性,MTT法检测其细胞毒性。裸鼠尾静脉iv给予QD-AFP-Ab复合物探针0.2μmo·lkg-1,观察裸鼠死亡情况并检测血清谷丙转氨酶(GPT)、谷草转氨酶(GOT)、尿素氮(BUN)和肌苷(Cr)水平,并采用四极电感耦合等离子质谱测定该探针0.1μmol·kg-1在裸鼠血清中的浓度及在各主要组织中的含量。结果QD-AFP-Ab复合物探针在水溶液中分散性好,当其浓度低于0.1μmol·L-1时,无明显细胞毒性。裸鼠尾静脉iv给予QD-AFP-Ab0.2μmol·kg-1均无死亡,血清GPT,GOT,BUN及Cr水平与正常对照组相比无显著性差异。该探针在裸鼠体内的循环半衰期约为2h;代谢24h后,主要分布于脾脏、肝脏及肾脏。结论QD-AFP-Ab复合物探针体外低于0.1μmol·L-1和体内0.2μmol·kg-1时未观察到明显的细胞毒性和急性毒性,具有较好的生物相容性,主要分布在脾脏、肝脏和肾脏,最终可能通过肾脏排出体外。OBJECTIVE To study the biocompatibility and toxic profiles of quantum dot(QD)-alpha-fetoprotein (AFP) antibody(Ab) probes. METHODS Mercaptoacetic acid modified CdSe/ZnS water-soluble QD was linked to mouse-anti-human AFP monoclonal Ab to form water soluble QD-AFP-Ab probes. The properties of these probes were studied through spectra analyses and transmission electron microscope. The cytotoxicity was measured by MTT assay. Nude mice were iv given QD-AFP-Ab probes 0.2 μmol·kg-1, and acute toxicity was observed until 7 d after administration. Glutamate-pyruvate transaminase (GPT), glutamic-oxalacetic transaminase (GOT), blood urea nitrogen (BUN) and creatinine (Cr) in plasma were detected. Concentrations and contents of QD-AFP-Ab in plasma and organs were detected by inductively coupled plasma-mass spectrometry after nude mice were iv given QD-AFP-Ab 0.1 μmol·kg-1. RESULTS QD-AFP-Ab probes had good water-solubility. When the concentration was less than 0.1 μmol·L-1, there was no significant cytotoxicity. No nude mice died after they were iv given QD-AFP-Ab probes 0.2 μmol·kg-1. Compared with normal control group, the serum levels of GPT, GOT, BUN and Cr were not affected significantly by QD-AFP-Ab probes. The half-life of QD-AFP-Ab probes was approximately 2 h. They were mainly distributed in spleen, liver and kidneys of nude mice after 24 h. CONCLUSION No significant cytotoxicity or acute toxicity are observed at QD-AFP-Ab probes less than 0.1 μmol·L-1 and 0.2 μmol·kg-1, and QD-AFP-Ab probes have good biocompatibility. QD-AFP-Ab probes are mainly distributed in spleen, liver and kidneys, and might be ultimately excreted by kidneys.

关 键 词：量子点 细胞毒性 急性毒性 代谢 

分 类 号：R318.08[医药卫生—生物医学工程]