【作者】 熊平；

【导师】 杨新明；

【作者基本信息】 中南大学 ， 肿瘤学， 2009， 博士

【摘要】 肿瘤靶向定位治疗是目前医学界研究的热点和难点问题。靶向定位的载体目前主要有抗体载体、配体载体、活性多肽载体等,定位原理都是基于生物学特性进行组织的,每一种载体对药物定向带有很大的选择性,都只针对特定的肿瘤治疗有效。随着现代科学技术的发展,纳米科技和纳米材料的科学价值越来越重要,其应用前景已被人们广泛认识。纳米技术在医学上的应用,产生了一门新的学科——纳米医学。本文首次提出了一种新型的定位治疗系统。并对可被定位于肿瘤部位治疗肿瘤的药物载体——顺磁放射性纳米铁核素,及其制备方法,和纳米粒子在人体血流中的受力情况、在外磁场作用下的聚集情况进行了论述。纳米铁核素的制备是采用羰基法制备纳米铁,然后通过脉冲中子反应堆辐照纳米铁得到顺磁纳米铁核素。结果：放射性核素—纳米铁的平均粒径<100nm,具有超顺磁性、放射性活度和较好的磁导向功能,可有效定位于靶区。当有外加磁场时,纳米铁粒子不仅受到血流中三种力的作用,还有磁场力的作用,而这个力在将纳米铁粒子聚集到病灶部位时起到关键作用,决定了纳米粒子的聚集状况。通过将血流动力、血液粘滞力、重力以及磁场力的矢量合成,分析出纳米粒子在血管中的运动状态,通过使用MathCAD和ANSYS软件的模拟实验,证明纳米铁粒子在血液中能有效的聚集到所需定位的病灶部位,达到有效的靶向治疗目的。将纳米铁有效地定位到病灶部位,关键是要在病灶部位形成一个强磁场区域,达到纳米铁汇集的条件。针对上述难点,本文作了以下几方面的工作：(1)介绍了电磁场的基本理论,分析了磁场定位靶向治疗肿瘤的可行性,并建立了三维旋转磁场定位治疗肿瘤的理论。(2)利用MathCAD软件计算各种条件下磁场的大小及其变化规律,应用ANSYS软件建立有限元模型进行磁场模拟。(3)纳米铁粒子在血流中(层流状态下)所受到的力主要是血流动力和血液粘滞力以及自身重力,通过分析血液的组成和性质、血液粘滞度、血管中的血流速度,推导出几种力的计算方法及计算模型。(4)计算三维旋转磁场所需参数,建立模型,通过实验验证理论所得结果。三维旋转磁场的模拟结果以及原理机的实际试验结果,均取得了良好的效果,为三维旋转磁场定位治疗仪投入工业化生产提供了理论依据。更多还原

【Abstract】 Tumor targeted therapeutic is the hot and difficulty point in mordern scientific world. The carriers of medical include antibody carrier, conjugant and active amylase carrier teal. The theoretic model is based on biology characteristic. Each drug has specific target and effect in specific tumor tissue.With the development of modern science and technology, the scientific value of nano-technology and nano-materials is increasingly important. Its application prospect has been widely recognized. The application of nanotechnology in medicine, and it has created a new subject-medical nanotechnology. This paper discuss a novel, location of the tumor can be treated with drugs-preparation of magnetic nanoparticles radioactive nuclides, the pressure when nano-particles in the blood of human and the circumstances of conglomeration by the effect of external magnetic field.Preparation Methods:carbonyl method to make nanoiron is adopted. Paramagnetic iron nanoparticles nuclides are obtained by radiating nanoiron after pulsed neutron reactor. Results:The average size of radio nuclides—nanoiron is less than 100nm; it has super paramagnetic, radioactivity and better magnetic function and can be effectively in the target location.When in the external magnetic field, the nanoparticles do not only effect by three roles pressure of blood, but also the strength of the magnetic field which will be the key role when nano-particles gathered at the part of focus and decide the gathering condition of nanoparticles. By synthesizing the three magnetic vectors in blood, blood viscosity, gravity and magnetic field, analyzing the movement of nano-particles in the blood vessels and using the soft of MATHCAD and ANSYS, the simulation results can effectively prove the location of iron nanoparticles aggregation in the blood vessel which we need. Targeted therapy can achieve this purpose.In order to orientate the drug carrier to tumor focus, it need to form a strong magnetic field gradient and satisfies the condition of the nanometer-iron particles aggregation. In order to solve the problem this paper sets forth following study:(1) This paper introduces the principle in the electromagnetic field, analysis the feasibility of target therapeutic by magnetic field gradient, establish the theory of rotated 3D magnetic field for targeted therapeutic of tumor.(2) This paper calculates the magnetic field intensity and the variety in different conditions using the MathCAD soft, simulate the model of magnet field using the ANSYS soft.(3) The major forces of Nano-particles in blood (laminar flow conditions) are the dynamic of blood flow and viscous forces and their gravitational force. By analyzing the composition and nature of blood, blood viscosity and velocity of the blood vessels, several calculation methods and former are deduced above.(4) The parameters were calculated and the model was designed. Validate the result by experiment.The result is well both in simulation and theoretical equipment. Gain the data for the for industry production.更多还原