The Molecular Assembly And Biological Activity Research Of Modified Cyclodextrin

Supramolecular chemistry, which is focus on the non-covalent interaction between molecules, is a type of interdiscipline composed of modern chemistry, material chemistry and life science. As the second generation of host compounds, the molecular recognition and assembly of cyclodextrin (CD) is the most important part in supramolecular chemistry. In this thesis, we constructed two types of supramolecular targeted anticancer drug delivery systems based on synthesized folic acid (FA) modified β-CD and/β-CD modified hyaluronic acid, respectively, and then we further valuated their antitumor activities in vitro and in vivo. In addition, we synthesized a novel bridged bis(permethyl-β-cyclodextrin)s with photochromic properties, and then investigated the photophysics and photochemistry properties of the assembly formed with porphyrin. The content of the thesis is as follows:1. Besides the introduction of supramolecular chemistry, we concluded the research progress in molecular recognition and assembly of cyclodextrin, and then generally commented the newest research achievements in design of targeted drug delivery systems based on supramolecular interactions.2. We constructed a nanosupramolecular assembly by FA-modified β-CD and GO noncovalently linked by adamantane-grafted porphyrin. The resulting quarternary supramolecular nanoarchitecture based on strong π-π stacking between the porphyrin and GO and the high hydrophobic affinity between β-CD and adamantane, can be employed as a targeted delivery system to efficiently carry doxorubicin to tumor tissues with low toxicity to normal cells under physiological conditions.3. A series of conjugated polysaccharide nanoparticle, named hyaluronic acid particle (HAP), composed of a hydrophobic anticancer drug core and a hydrophilic HA shell was successfully constructed by host-guest interaction between β-CD-modified HA and adamplatin prodrug. The resultant nanometer-sized HAP could recognize HA receptors over-expressed cancer cells. Biological experiments demonstrated that HAP exhibited similar anticancer activities to, and lower side effects than commercial anticancer drug cisplatin in vitro and in vivo.4. We synthesized a novel dithienylethene-bridged bis(permethyl-β-cyclodextrin)s. Taking advantage of the high affinity between host compound and porphyrin derivant, we conveniently constructed a linear supramolecular architecture and carefully studied the light-controlled fluorescence resonance energy transfer process through host-guest interaction by means of fluorescent spectrometry.