Drug And Gene Carriers Based On Metal-Organic Frameworks And Chitosan Nanoparticles

Constructing effective drug/gene delivery nanocarriers is one of the most significant progress in tumor therapy and disease prevention. By using nanomaterials as delivery carriers, drugs/gene can be assembled on the surfaces or encapsulated in the interior of these nanomaterials to form delivery systems. When the systems are exposure to the appropriate stimuli, the loaded drugs/gene can be released in a controllable fashion. The nanomaterial based delivery was protected the drugs/gene from premature release and reducing the adverse side effects of the drugs, which led to a great potential to revolutionize cancer therapy and disease prevention. Aiming at nanocarrier based drug/gene delivery, this thesis mainly focuses on the development of metal-organic frameworks and chitosan nanocarrier for drug/gene release. 1. Encapsulating antitumor drug into a metal-organic frameworks material for intracellular acid-triggered drug deliveryThis section proposed a metal-organic frameworks ZIF-8 nanocarrier encapsulated antitumor drug for intracellular acid-triggered drug delivery. In this system, the zeolitic imidazolate framework, a metal-organic frameworks formed by 2-methyl imidazolate and zinc ions, was chosen as the host material for drug delivery. Doxorubicin (DOX), as a model drug, was encapsulated in ZIF-8 structures to assess the drug release behaviors and tumor therapy. At neutral pH, due to the small window size of ZIF-8, DOX are confined within the frameworks, resulting in blockage of pores and package of DOX. However, the slightly acidic environment would lead to the dissociation of coordination between the zinc and imidazolate ions, giving rise to degradation of ZIF-8 and the subsequent release of the entrapped drug. Evaluation of DOX-encapsulated ZIF-8 nanoparticles in the HT-29 human colon cancer cell line demonstrated cell internalization and cyto toxic ity. We demonstrate that the DOX-encapsulated ZIF-8 nanoparticles show enhanced cell death, indicative of internalization and intracellular release of the drug, thereby rendering the ZIF-8 scaffold an ideal drug delivery vehicle. 2. Study on the effect of TPIL-218 fusion gene in mice using chitosan nanoparticles as nanocarriersIn this section, chitosan was used nano material of gene vector. The electrolytic polymer was formed with electrostatic interaction of chitosan to adsorb fusion gene TPIL-218 for researching on disease prevention and immune responses. In this experiment, Tibetan pig cytokine Interleukin 2 and 18 were used the materials to construct fusion gene TPIL-218 with recombinant DNA techniques. The fusion gene was cloned into plasmid pcDNA3.1. Then the recombinant plasmid was entrapped with liposome and transferred into Cos7 cell. The fusion gene TPIL-218 was highly expressed in Cos7 cells and the expression product of the gene has biological activity. The plasmid and chitotan nanoparticles which can effectively transfected animal cells were polymerized. The expression in vivo of chitosan nanoparticle aggregation wrapped TPIL-218 fusion gene and its effect on immune activity were studied after the fusion gene was inoculated mice. Theresults showed that the fusion gene TPIL-218 was successful gene construction, can enhance the immune effect of the fluid in mice. Chitosan nanoparticles as a nano gene vector could significantly improve the expression level of the exogenous TPIL-218 gene in vivo and significantly enhanced the humoral immune response in mice.