Design,synthesis Of Nitric Oxide Controlled Release Magnetic Nanoparticles And Study On Targeted Therapy For Hepatic Tumor

Nitric oxide（NO）,as an endogenous diatomic free radical,plays an important role in inhibiting tumor growth and metastasis.It is antitumor effect largely depends on its release location,local concentration and contact time.Therefore,it is of great significance to develop a nano-carrier platform which can target tumor cells,increase NO loading and control to release.Based on above considerations,we developed a new type NO controlled-release magnetic nanoparticle（NP）using a single system to reach the target site in multiple ways to improve NO targeted transport capacity.The main contents of this thesis include:The first chapter reviews the physiological effects and antitumor mechanism of NO,the potential applications of some NO donors and carriers in the field of biomedicine in recent years.The second chapter focus on the design,synthesis and characterization of the Fe₃O₄@S-nitrosothiols-HA-FA complex.Fe₃O₄ as the core of NP was measured the hysteresis curve,it is confirmed that the NP shows superparamagnetic properties.Distillation precipitation polymerization was used to cross-link the polymer on the surface of the magnetic core,and then the two target molecules,hyaluronic acid（HA）and folic acid（FA）,and S-nitrosothiols as NO donor were modified on the surface of NPs through covalent bonding.The sturcture of NPs was successfully characterized by transmission electron microscopy,elemental analysis,infrared spectroscopy,and thermal weight loss.In the third chapter,the bio-targeting study of dual-targeted NO controlled-release magnetic NPs was carried out.The NO release behavior of NPs was measured by the classical Griess reagent method,which proved that the nanoparticles had good stability during the circulation in vivo,and could release high concentrations of NO quickly under certain triggering conditions.Confocal and cytotoxicity experiments confirmed that HA-co-FA modified S-nitrosothiol magnetic NPs show active tumor cell target recognition in vitro and reduce the survival rate of liver cancer cells.From the results of magnetic resonance imaging（MRI）characterization,organ and tumor biodistribution measurements,the prepared NPs have significant enrichment at the tumor site.The data of treatment experiments on liver cancer mice and systemic toxicity tests show that NPs inhibit tumor growth and are biologically safe.we believe that the tumor targeting system with external magnetic field targeting and HA-co-FA active induction synergy can be used as a new type of potential nanomedicine platform.