两种近红外荧光探针的合成及肿瘤靶向研究  

Synthesis and Tumor Targeting Research of Two Near-Infrared Fluorescence Probes

作　　者：邓大伟[1] 刘飞[1] 曹洁[1] 陈新洋[1] 顾月清[1] 

机构地区：[1]中国药科大学生命科学与技术学院,江苏南京210009

出　　处：《中国激光》2010年第11期2735-2742,共8页Chinese Journal of Lasers

基　　金：国家自然科学基金(30800257;30700779和30970776)资助课题

摘　　要：合成了两种近红外有机荧光探针,即叶酸-PEG-ICG-Der-01和LDL-ICG-Der-02,它们分别以肿瘤表面高度表达的叶酸受体以及低密度脂蛋白(LDL)受体为靶点。探针复合物中的叶酸和低密度脂蛋白部分为探针分子提供靶向"导向",通过化学共价键分别与有机近红外染料ICG-Der-01和ICG-Der-02偶联,近红外染料则为探针分子的荧光信号输出端。利用紫外分光光度计、近红外荧光光谱仪及近红外荧光成像系统分析这两种荧光探针的光学性质,以及它们在叶酸受体及LDL受体过度表达的肿瘤鼠体内的成像过程。结果显示,所合成的叶酸-PEG-ICG-Der-01和LDL-ICG-Der-02探针的荧光强度及光稳定性都高于对应的染料单体。而体内成像结果则表明两种探针都保持了叶酸和LDL的生物活性,能有效地靶向到相关肿瘤部位,成像清晰,并且能最终代谢排出体外。比较这两种探针,叶酸-PEG-ICG-Der-01对肿瘤细胞的靶向性要优于LDL-ICG-Der-02,并能用于肿瘤早期诊断。Two near infrared fluorescence probes（i.e.,folate-PEG-ICG-Der-01 and LDL-ICG-Der-02） are synthesized.Here,over-expressed folate receptors and low density lipoprotein（LDL） receptors in some specific tumors are chosen as target.The residues of folic acid and LDL,as the targeted ligand,are covalently conjugated to organic near-infrared fluorescence dye ICG-Der-0 and ICG-Der-02 respectively,where near-infrared dyes are the output of fluorescence signal.The optical properties of the two probes are characterized by ultraviolet spectrophotometer and near-infrared fluorescence spectroscopy system.The imaging process of folate-PEG-ICG-Der-01 and LDL-ICG-Der-02 probes in tumors which over expressed folate receptors and LDL receptors is further detected by near-infrared fluorescence imaging system.The results show that as-prepared folate-PEG-ICG-Der-01 and LDL-ICG-Der-02 probes present higher fluorescence intensity and better photo stability than those corresponding near-infrared fluorescence dyes.And the results of in vivo near-infrared fluorescence imaging confirme that these two probes are highly bioactive,can efficiently target tumor sites,and finally be eliminated.Compared with LDL-ICG-Der-02,the targeting capability of folate-PEG-ICG-Der-01 probe is more effective,and has great potential in non-invasive real time early tumor diagnosis.

关 键 词：医用光学 近红外荧光成像 光学分子探针 肿瘤靶向 叶酸 低密度脂蛋白 

分 类 号：R318[医药卫生—生物医学工程] R979.1[医药卫生—基础医学]