Using A Click Reaction To Prepare Nanomaterials For Biomedical Applications

Click chemistry refers to a philosophy of how to do chemistry. It utilizes a series of reliable, efficient, selective and modularized chemical reactions for the rapid synthesis of new useful compounds containing heteroatms. It especially emphasizes on the discovery of novel combinatorial libraries through the formation of heteroatom links.Among this group of reactions, or so called "click reactions", some typical examples are included, such as Cu(I)-catalyzed azide-alkynyl cycloaddition, Diels-Alder reaction and thiol-ene coupling reaction.Rapid developments have been realized for click chemistry in many scientific research fields due to its various inherent properties.A novel biocompatible click condensation reaction based on cyano-cysteine is able to form a stable five-member thiazole ring under physiologic conditions in the absence of any catalysts.In this dissertation, we designed a series of AB2-type small molecules, which condense to form oligmers under physiologic conditions. The formed oligmers then self-assemble into nanoparticles with supramolecular structures due to intermolecular π-π stacking.The residual thiol groups on the surface of the nanoparticles were oxidized to form disulfide bonds, and generated insoluble cross-linked polymers which could be reduced back to oligmers by reductants.Abundant reactive cysteine residuals on the surface of nanoparticles could also react with cyano-terminated FITC to construct a fluorescence capturing nanoprobes for signal turn-on. The enhancement of fluorescent signal is able to be directly observed with a small animal imaging. In the meantime, the fluorescence nanoparticles are able to simulate cell behaviors, and the fluorescent signal is able to be monitored by flow cytometry.Based on the same click reaction, we synthesized the dendrimer with N-bis-cysteinyl ethanediamine core and AB2-type small molecule precursors. The possibility of further modification on the surface of the dendrimers to enable them with the functions of both targetting and carrying the MRI contrast agents indicates the dendrimer to be a promising candidate for tumor diagnosis.