Synthesis And Properties Of Active And Passive Targeting Stimuli-responsive Polymeric Drug Carriers

Nowadays, cancer has been one of the leading causes of death, and the incidence of cancer continues to increase. The cancer is a disease caused by uncontrolled cell growth, due to participate in the balance of cell proliferation and cell death gene mutation, making the organization's balance disrupted. Because of its specificity, chemotherapy has proven partially successful in the treatment and prolonging the lives of patients. In recent years, the controlled release nanosystems based on a wide range of materials, capable of selectively releasing cargo have attracted great attention because it is not only reduce the toxicity of small molecules drug and prolong circulation time, but also enhance accumulation in the tumor sites via the enhanced permeability and retention(EPR) effect, decreased adverse effects, and improved drug tolerance.Smart polymeric nanocarriers have been extensively investigated in the field of drug delivery systems. Especially the targeted group is grafted onto the carriers which makes chemotherapy drugs arrive the cell surface receptor directly. we prepared stimulus responsive amphiphilic polymer micelle and silica nanoparticle carriers and their performance for drug research.The thesis consists of two chapters as follows:1.The passive targeting P(Ma-Hydrazone-TMBA)-b-PHPMA and active targeting P(Ma-Hydrazone-TMBA)-b-PHPMA-b-PFA active targeting polymer carriers were prepared by RAFT polymerization. Methacryloyl chloride was reacted with p-nitrophenol formated hydrophobic polymer monomer MA-Nop, and use RAFT polymerization become hydrophobic block. Then, the amphiphilic block copolymer was prepared by N-(2-hydroxypropyl)methacrylamide(HPMA) polymerization.The folate targeting group monomer was initiator polymerization to form triblock polymers, and modified on the polymer to form a polymer having active targeting hydrazone bond. The synthesizing a block copolymer, micelle formation, and its release properties were characterized by 1H NMR, TEM and UV, at last the cell experiment was characterized by laser scanning confocal microscopy.2.Synthesis of active and passive targeting of mesoporous silica nanoparticles drug carrier. By grafting APS in the mesoporous silica surface, so that the tube having an amino functional group, through the ammonia decomposition reaction of methacryloyl chloride and introduce a double bond. HPMA, folic acid monomer and modified 2, 2- diethanol disulfide cross-linking agent to initiate the polymerization by different time, the resulting surface contains targeting group nanoparticles drug carriers. Characterize the polymerization of monomer and polymer graft of silica spheres, measuring release performance by fluorescence spectroscopy, 1H NMR, TEM, UV, IR and other means.The half inhibition rate of silicon to Hela cells toxicity tests and cell imaging experiment confirmed such a carrier can not only significantly reduce the small molecule drug toxicity, and inhibition of tumor cells remain, especially targeting group use groups, so that the amount of drug accumulation increased significantly.