Construction Of Nano-supramolecular Systems And Their Biological Applications Based On Cyclodextrins

Supramolecular chemistry is a type of interdiscipline composed of chemistry, material chemistry, information science and life science, etc. As the second generation of host compounds, molecular recognition, molecular assembly and thermodynamics of cyclodextrin (CD) and its derivatives are significant parts of supramolecular chemistry. In the thesis,β-cyclodextrin derivatives bearing quinoline, naphthol groups were synthesized for the investigation of their binding modes towards some biomolecules. we investigated the DNA cleavage ability of this pseudopolyrotaxane based on cyclodextrins and C6o. In addition, two gold supramolecular anticancer drug delivery systems were constructed based on cyclodextrin-modified hyaluronic acid and cyclodextrin-modified biotin. And then we valuated the ability of anti-tumor in vitro. The contents of the thesis are as follows:1. The general aspects of supramolecular chemistry and cyclodextrin were described briefly. The new progress and achievements based on molecular recognition and molecular assembly were concluded. We also concluded the new progress and the newest achievements in biological medicine field based on cyclodextrin and gold nanoparticle.2. The molecular binding behaviors of four β-cyclodextrin derivatives bearing quinoline and naphthol groups with bile salts,(±)-borneol and (±)-camphor were studied in aqueous buffer solution (pH7.20) by means of microcalorimetrical titration,2D NMR spectroscopy and molecular modeling. Thermodynamically, the host-guest binding behaviors were mainly driven by the favorable enthalpic changes, accompanied by the unfavorable entropic changes, and the hydrogen-bonding interactions and van der Waals interactions were the main driven forces governing the host-guest binding.3. We designed and synthesized a novel PDT (photodynamic therapy) photosensitizer based on pseudopolyrotaxane with cyclodextrins and C60. C60was covalently grafted to β-cyclodextrin (β-CD) to form water-soluble pseudopolyrotaxane. Then we investigated the DNA cleavage ability of this pseudopolyrotaxane under visible-light irradiation.4. Through the high affinity of β-cyclodextrin (β-CD) cavity and adamantane moiety, a novel polysaccharide-gold nanocluster supramolecular conjugate, HACD-AuNPs, was successfully constructed from gold nanoparticles (AuNPs) bearing adamantane moieties and cyclodextrin-grafted hyaluronic acid (HACD). Possessing a holey structure, the resultant supramolecular conjugate could serve as a versatile and biocompatible platform for the loading and delivery of various anticancer drug, such as doxorubicin hydrochloride (DOX), paclitaxel (PTX), camptothecin (CPT), irinotecan hydrochloride (CPT-11), and topotecan hydrochloride (TPT), taking the advantage of the controlled association/dissociation of drug to the cavities formed among the HACD skeletons and AuNPs cores as well as the efficient target ability of hyaluronic acid to cancer cell. Significantly, cell viability experiments revealed that this drug delivery system exhibited similar tumor cell inhibition ability, but fairly lower toxicity than free anticancer drug owing to the hyaluronic acid reporter-mediated endocytosis.5. Benefiting from the high affinity of β-cyclodextrin cavity and adamantane moiety, a novel supramolecular nanocluster was successfully constructed with gold nanoparticles bearing adamantane moieties and cyclodextrin-modified biotin. The resultant gold nanocluster could serve as biocompatible scaffold for the loading and delivery of an hydrophobic anticancer drug paclitaxel (PTX) with its holey structure. The release rate of PTX from supramolecular conjugate was pH-dependent, thus it increased remarkably in mildly acidic environment whereas maintained a sustained manner in physiology environment.