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Preparation And Application Of Lymph Targeted Magnetic Resonance Imaging Contrast Agents

Posted on:2018-02-08Degree:MasterType:Thesis
Country:ChinaCandidate:Y QiaoFull Text:PDF
GTID:2381330596490087Subject:Materials engineering
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Lymphoma is a major disease which is harmful to human beings currently,and it is also called malignancy.High cost of treatment,difficulty to be cured,found that the cause of the delay and so on to bring a lot of trouble and pain.Therefore,early diagnosis and treatment in the early stage of lymphoma is an important way to prevent the development of tumor and reduce the recurrence and metastasis of the tumor.But nowadays,there are still many disadvantages in contrast agent based on enhanced permeability and retention effect(EPR effect),which mainly manifested in low specific combination of lymphoma,lymphatic vessels have no active transport process on the contrast agent,and so on.So to improve the imaging effect and shorten the imaging time is the direction of the current lymph node targeted contrast agent.In this paper,all of nano-probe is soft material CTS and hard material gold nanorod,two kinds of multifunctional lymphatic targeting contrast agents were designed,and they were applied in the diagnose and treatment in lymphoma.The main contents of this paper are as follow:(1)In the aspect of soft matter,we chose chitosan CTS as matrix material to conduct a series of diagnostic studies.The surface is connected with the chitosan nano spheres which are connected with the macromolecular hyaluronic acid(HA),and the Gd ion is added by the complexation action,the prepared HA-CTS-Gd nanosphere is a MRI contrast agent which could target to lymphoma.The cell experiments and release of Gd ion indicate that HA-CTS-Gd nanospheres have excellent ability of lymphatic targeting and good biocompatibility.The MRI in vitro and in vivo indicate that by intravenous injection of 10 min,the nanoparticles can be injected into the mouse tumor region through blood circulation,and the tumor region of mice can be effectively imaged at least 50 min.(2)In the hard material aspect,we choose mesoporous silica as the matrix material.Gold nanorods were encapsulated with mesoporous silica and Mn ions were mingled in,then macromolecular hyaluronic acid was linked to the surface of mesoporous silica and DOX was loaded in,so multifunctional probe combined diagnose and treatment Gold Nanorods@mSiO2@Mn@HA-DOX(GNR@MMHD)nanoparticles were prepared and which possess the function of lymph target.The temperature of solution dispersed with nanoparticles could reach 65?by 980 nm near infrared laser with 3w/cm~2 power of 5 min in vitro and in vivo.The cell experiment in vitro showed that the nanoparticles had low cytotoxicity and good lymphatic targeting,combined with the laser irradiation and the loading of doxorubicin,the proliferation of tumor cells could be suppressed effectively.In vivo and in vitro magnetic resonance imaging results show that the nanoparticles have good magnetic resonance imaging ability.Finally,the tumor inhibition experiment in mice showed that the nanoparticles combined with hyperthermia and chemotherapy could effectively inhibit the growth of tumor.In this paper,based on the soft material CTS and hard material GNR,the diagnosis of lymphoma was made,the function of magnetic resonance imaging was made by doping Gd or Mn ions,the ability to target the lymphoma by connecting the hyaluronic acid.And the gold nanorods were loaded with doxorubicin in the mesoporous silica,so that it had the function of heat chemotherapy,and the effective inhibition of lymphoma was achieved.The research results of this paper are of great significance to the early diagnosis and treatment of lymphoma.
Keywords/Search Tags:lymphoma, magnetic resonance imaging, hyaluronic acid
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