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题 目：Real time investigation of the biomolecules by using fluorescent imaging
荧光成像法：生物分子的实时探测
主 讲 人：Dr. BenGang Xing
Division of chemistry and biological chemistry SPMS, NTU
主 持 人：卜宪章 副教授
中山大学药学院
时 间：2006年12月26日（星期二）上午10：00
地 点：中山大学北校区动物中心八楼学术报告厅
广州市中山二74号
中山大学医学科学处
中山大学药学院
2006-12-21
摘要：
Fluorescent imaging has currently attracted a great deal of academic attention in the field of biological and cellular research because of their extremely significant detection efficiency, high sensitivity, low cost and relatively simple to use. As a promising modality in molecular imaging, fluorescent techniques have been widely employed to monitor the gene expression, tumor proliferation and cellular development in vitro and/or in the culture. To real time monitor these biological pathways, many of biological molecules as reporter have been successfully developed. All the biological phenomena can be easily read out only in vitro or cells through the native fluorescent property of reporter like green fluorescent protein (GFP), or the fluorescence changes after the reaction of these biomolecules (beta-galactosidase, alkaline phosphatase etc) with the individual substrates. However, one unified reporter which can be used not only in vitro, but also in the cell culture and living subjects as well has not been available yet.
Beta-lactamases (Bla) are a family of bacterial enzymes that have been well characterized because they can efficiently cleave penicillins and cephalosporin and cause the bacterial resistance to β-lactam antibiotics. Rapid and sensitive detection of β-lactamase activity in biological samples is thus of large clinical importance. Because of their relative small size and monomeric properties and non-toxicity in eukaryotes cells, β-lactamase has already been developed as a reporter for examining the promoter/regulatory elements activity in living mammalian cells. In this study, we developed a series of novel β-lactam based NIR fluorescent probes based on the fluorescent energy resonance transfer (FRET). By using infrared imaging techniques, we demonstrated the specific uptake of the probes in the tumor which can highly expressed β-lactamase. The cell-permeability, higher sensitivity and stability of the tracers made them possible to be used as biosensors to image β-lactamase not only in vitro, in single living cell but also in the living animals.