Study On The Macromolecule Vesicles And Drug Loaded Nanogel Based On Nature Polymer

In supramolecular chemistry, molecules are connected through noncovalent linkages, such as hydrogen bonds, electrostatic interactions, hydrophilic-hydrophobe interactions, to create a ordered structure. Living systems make use of this concept extensively. For example, the cell cytoskeleton in which long ordered filaments of protein monomers; cell membrane is assembled by phospholipid and protein. Since90th last century, research about the polymer vesicle which is one kind of supramolecular chemistry developed very fast. Many kinds of molecules were used to assemble vesicles by hydrophilic and hydrophobic interactions. At the same time, artificial vesicles which have similar structure with cell membrane are widely investigated. Moreover, for the special structure of the polymer vesicles, they have high potential in several applications. In recent years, our group reported "Polymer-Monomer Pair" strategy for preparing nanoparticles, by initiating the polymerization of small molecules in water when nature polymer with opposite charges were existent.In this thesis, The heparin (HEP) or chondroitin sulfate (CS) were chosen as proton-donating polymers and2-(diethylamino) ethyl methacrylate (DEA) monomer were chosen as proton-accepting. By controlling the reaction condition and ratio of reactant, a series of vesicles were prepared. The details of the vesicle research are described as below. 1) When the HEP dissolved in water, the DEA was added to the solution, ionic bonding between HEP molecules and DEA formed. After the initiation and DEA was polymerized. The HEP-PDEA electrostatic complexes will assemble to nano-vesicles. And we cross-linked them to improve the stability.2) We change the HEP with CS molecule to decrease the hydrophilic groups, and the CS-PDEA vesicle size stretch across an unusual vast range, from nano-scale to tens of micrometers. The real-time fusion of CS-PDEA vesicles could be observed and the details of vesicle fusion were researched. And we think the defects of membrane is the main reason of the vesicle fusion. The experiment of osmotic pressure response confirmed the existence of defects, and fusion induced by NaCl is further proof that defects induce fusion. Vesicle fission was also achieved by addition of amino acid to vesicle aqueous solution. This work helps to understand the vesicle fusion and fission.3) Wall-super-thick giant multilamellar CS-PDEA vesicles were successfully prepared through hydration of CS-PDEA film. The formation process of multilamellar CS-PDEA vesicles included formation of CS-PDEA compound vesicles, multifusion of small vesicles in the compound vesicles and rearrange of the vesicle membrane. The whole process was remarkably simple and moderate, and no using of organic solvent was significant in ecological sense. For the membrane of the vesicles was semipermeable, we encapsulated the yeast cells into the CS-PDEA vesicles and achieved remarkable success. Cells were well protected by the vesicles from lysozyme.4) For the good biological functions of HEP molecules, and disulfide bonds are sensitive at tumor cells. We connected alkene at the HEP molecules, and cross-linked them with cystamine bisacrylamide (CBA) which have disulfide bonds. Then HEP-CBA nanogel formed. The HEP-CBA nanogel was used to load agents. Through the experiments of drug release, cytotoxicity, living imaging, vivo distribution and antitumor, we found the HEP nanogel have good performance in tumor accumulation and antitumor activity.