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2013年中国药学大会暨第十三届中国药师周

作者： Meng-Jie Gu Kun-Feng Li Nai-Qi Fu Zhen-Jun Yang Zhuo-Zhao Zheng Tian-Yuan Fan State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University Department of Radiology Peking University Third Hospital

Objective: To develop MRI contrast agent for diagnosis of tumor, aptamer-targeted paramagnetic liposomes were designed and prepared. Liposomes containing new membrane-bound polychelator possess enhanced relaxivity for water protons resulting in an increase of tissue signal intensity on MR images, compared with commercial MRI contrast agents containing gadolinium, such as DTPA, DOTA, Gd-DTPA-SA and Gd-DTPA-PE. GBI-10 is a single-stranded DNA （ssDNA） aptamer for tenascin-C （TNC）, which distributes on the surface of tumor cells as a dominant extracellular matrix protein. The GBI-10-targeted liposomes （GTLS） can recognize the TNC on the tumor cell surface, which will be helpful for the development of new convenient and sensitive in vitro diagnostic assays for tumor. This study evaluated the in vitro performance of an aptamer-targeted paramagnetic liposome formulation--GTLS, as a contrast agent for MR-based image guidance applications. Methods: In this study, pre-targeted liposomes （PLS） containing Gd-DTPA-BSA, DSPC, cholesterol, DSPE-mPEG 2000 , and DSPE-PEG 2000 -COOH was produced by lipid film hydration and extrusion, and GBI-10 aptamer was covalently conjugated to the distal end of DSPE-PEG 2000 -COOH lipid by amide bound and loaded onto PLS surface as the targeting ligand to form GTLS. Then non-targeted liposomes （NTLS） containing Gd-DTPA-BSA, DSPC, cholesterol, DSPE-mPEG 2000 was prepared using the same method. Here NTLS served as a control. The particle size and zeta potential of GTLS and NTLS were determined with dynamic light scattering at room temperature. To confirm the efficacy of GTLS targeting C6 cells （glioma cell line）, coumarin-6 was used as a fluorescent probe and separately encapsulated in GTLS and NTLS, the fluorescent images of the cells were analyzed using a TCS SP2 confocal microscope. In addition, the imaging efficacy of PLS and NTLS were assessed in vitro using a clinical 3.0 Tesla MR scanner at room temperature. The longitudinal relaxivities of

关键词： Magnetic resonance imaging Contrast agent Gadolinium Liposomes GBI-10 aptamer tumor targeting

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Selection of DNA aptamer that specific binding human carcinoembryonic antigen in vitro

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Journal of Nanjing Medical University 2007年第5期21卷 277-281页

作者： Lifeng Wang Baorui Liu Haitao Yin Jia Wei Xiaoping Qian Lixia Yu Department of Oncology Drum Tower Hospital Affiliated to Medical School of Nanjing University Nanjing 210018 Jiangsu Province China

Objective：To select the specific aptamer of carcinoembryonic antigen （CEA）, one of the most attractive molecule for cancer target therapy and imaging. Methods： Seven rounds in vitro selection were performed against the purified CEA protein. Ligand-mediated target purification and Co-immunoprecipitation were adopted to verify the specific binding of the aptamer to the purified and native protein separately. Results：The CEA-specific aptamer which can bind both the purified and native protein with the high specificity was obtained. Conclusion：This is the first time the CEA specific apatmer was produced. The results in this study provides the preliminary evidence for further investigation and application of CEA-aptamer in the future.

关键词： aptamer carcinoembryonic antigen tumor targeting

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