Nanomedicine Research Based On Ferumoxytol

Medicinal iron based nanomaterials is characterized as extraordinary magnetism,nanosize and high biocompatibility with great research value,which is widely used as MRI contrast agents,tumor hyperthermia and nanocarrier medicine for clinical research.Ferumoxytol?FMT?is the representative product among these materials,as one kind superparamagnetic iron oxide nanoparticles?SPIONs?,approved by FDA in 2009 for the treatment of iron deficiency anemia in patients with chronic kidney disease,also exclusive SPIOs applied in clinical research.Its security and effectiveness in biomedical field has been confirmed.However,FMT faced many problems such as imperfect crystal properties and finite magnetic properties in single particle,having difficulty in achieving the various growing demand for clinical research.In order to improve the performance of FMT and expand the biomedical application,systematic research on FMT preparation and product properties is carried on.Based the common FMT production,we develop the technology for high performance FMT by magnetically internal heat coprecipitation and program cooling process co-precipitation for uniform and extremely small iron oxide nanoparticles.Then taking advantage of the above methods,various novel nanomedicine system based on FMT is established,including research on multimodal imaging,oral iron supplement and tumor hyperthermia chemotherapy.The following points are mainly involved in the dissertation:?1?Based on the principle of co-precipitation and the long-term experience of using magnetic field to prepare magnetic nanomaterials in our group,the reaction strategy of water cooled internal heat assisted co precipitation?HMIHC?was proposed,then high performance FMT has been prepared via this method.On the basis of the industrial preparation of FMT route and detection method,the new technology for the preparation of FMT by magnetic internal heat assisted chemical coprecipitation is developed by using magnetic fluid in the alternating magnetic field because of hysteresis loss and relaxation loss.Compared with the conventional heating method,magnetically internal heat greatly improves the sensitivity of temperature regulation and the heating uniformity during particle growth.Accompanied by a long time of hydrocooling circulation,the crystal realizes regular growth,achieving good crystal properties and interface properties.Under the action of alternating magnetic field in periodic changing direction,the magnetic moment orientation of particles gradually changes from disorder distribution to regular chiral arrangement,and the magnetization performance is significantly improved.As-synthesized FMT has the strongest magnetic response ability among the similar product.HMIHC offers an innovative strategy for high performance magnetic nanomedicine fabrication.?2?Based on FMT structure composition and FMT co-precipitation with independent intellectual property rights,programmed cooling coprecipitation to control the nucleation technology is proposed,for preparing extremely small iron oxide nanoparticles?ESIONs?in uniform size for T1MRI research.For further improve the clinical radiography function of FMT and expand its application,adopting the suitable starting temperature,starting material combination and injection mode,using program cooling to change cooling rate to obtain ESIONs?around 3 nm?.Compared with the common FMT,T1-MR imaging performance of ESIONs is significantly enhanced and altering as pH varies,also can be effectively labeled into the stem cells,expected to play an important role in clinical research fields such as clinical stem cell tracing and tumor theranostics.?3?Development of novel nanomedicine system based on FMT available in clinical field.In order to expand the clinical indications of FMT and develop new biomedical applications,FMT oral iron supplement and FMT coated by medicinal chitosan loading with DOX?DOX@FMT@Medicinal chitosan?for thermal chemotherapy is designed.A new kind of cellulose oxide nanomaterials?Fe₃O₄@CMC?was developed for the first time.Compared with FMT,the effect of two groups on iron deficiency in rats with iron deficiency anemia and the effect on the intestinal microecology of rats is studied.It is found that the two kinds of oral nanoscale iron has good effect of iron supplementation on iron deficiency anemia rats,and also presents a positive effect on intestinal microecology.The novel DOX@FMT@Medicinal chitosan has the properties of sol-gel transition and slow releasing drug in vitro.It is also discovered to have excellent therapeutic effect on tumor in vitro,having great potential for clinical application.