Application Of A Novel Fluorescent Probe Derivated From Pamam Dendrimer

Cancer has been one of the most deadly diseases recently, this includes liver cancer, lung cancer, breast cancer, for the sake of its high mortality, cancer has endangered the health of people in China and all over the world. Currently, there are various cancer therapies, among which operation is the most common treatment clinically, thus, precise location of tumor lesion during operation is of great importance. After several years’research, fluorescent tumor probe successfully solved this problem. There have been a couple of the probes being utilized clinically. Now, the main fluorescent probes that are clinically used are composed of antibodies and fluorescent molecules. However, these probes have several deficiencies.In order to solve all the problems, experts have put forward many novel fluorescent probes, which, unfortunately, all have deficiencies. For example, low activity fluorescent molecules are unlikely to be linked onto vectors, ligands usually can only bind to one target. In this project, we choose dendrimer, which is a dendritic macromolecule, as vector, this material is greatly stable, furthermore, when linked with C12lipid chains, it can absorb large quantity of fat-soluble fluorescent molecules. This project was designed to take advantage of the characterisity of the fat linkers to avoid commonly covalent conjugation. Then we modulated the surface of dendrimer using PEG, c(RGDfK), which can target tumor cells that express integrin αvβ3, was linked on the terminal of PEG then, finally, coumarin was incorporated into dendrimer physically, based on this procedure, we successfully synthesized four probes G4-25%C12-(mPEG5000)16-(RGD)8/coumarin,G4-25%C12-(mPEG5000)24-(RGD)8/coumarin, G4-25%C12-(mPEG2000)16-(RGD)8/coumarin, G4-25%C12-(mPEG2000)24-(RGD)8/coumarin. After in vitro experiments, we finally studied the influence of the number and length of PEG have on the efficiency of the probe, and found an optimal fluorescent probe. We also synthesized a kind of small-molecular probe, FA-Lys(FITC)-Val-Cit-Lys(DABCYL)-OH. After in vitro experiments, we found the small-molecular probe having a high targeting character like the macromolecule. But the small-molecular probe isn’t flexibility because the fluorescence molecule in the small-molecular probe is connected to carrier by chemical coupling and can’t be changed once connection.