顺磁纳米铁核素（PNINs）的物理靶向和富集特征研究
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摘要
目的：研制既可用作肿瘤靶向放疗的放射源,又可作为靶向化疗药物载体的新型材料——顺磁纳米铁核素(PNINs);设计体外旋转磁场系统作为引导磁场将PNINs定位于靶区,对引导磁场作用下PNINs的输运特性和靶向聚集特征进行理论研究与数值模拟,探索可适用于实体肿瘤靶向治疗的PNINs药物物理靶向定位系统,为临床应用提供理论依据和技术参数。
方法：(1)采用化学羰基法制备纳米铁微粒,然后通过脉冲中子反应堆辐照纳米铁制备顺磁纳米铁核素(PNINs);(2)在比较圆形电流磁场、亥姆霍兹线圈磁场、圆柱形永磁场、圆电流磁场和旋转磁场中添加导磁材料后的磁场强度和磁场梯度的分布特点后,对顺磁纳米铁核素(PNINs)在稳恒磁场(靶区)和旋转磁场(体外)引导下的物理靶向定位系统进行理论建模并采用ANSYS软件进行数值计算；(3)根据PNINs在体内的受力情况,建立其在靶向定位系统中的理论模型,利用MATHCAD程序对PNINs磁性药物颗粒在旋转磁场作用下的运行轨迹进行数值模拟；(4)对微血管中单个的顺磁纳米铁核素(PNINs)粒子和包裹有药物的顺磁纳米铁核素(PNINs)微粒在引导磁场作用下的输运特性、富集特征及动力学运动行为进行描述、建模和数值计算。
结果：(1)制得平均粒径<100nm的放射性核素-纳米铁,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；(2)在三种引导磁场中,圆柱形永磁体的磁场分布具有相对较大的磁场强度和梯度,添加导磁材料后,能提高靶区的磁场梯度,促使PNINs局效地聚集靶区,这对靶向治疗至关重要；(3)体外旋转磁场物理靶向定位PNINs,可避免有创伤性的体内靶区稳恒磁场靶向定位；(4)获得了磁性药物的粒径大小、PNINs含量、肿瘤深度、血流速度和血管直径等因素对药物收集率的影响关系。
结论：PNINs及其载药微粒在物理靶向定位系统包括体内恒磁场和体外旋转磁场作用下,能够在靶区高效聚集,具有优异的靶向性；其靶向聚集效果可以通过计算PNINs药物的收集率和俘获截面系数进行定量评价。
Objectives:To develop a new type of material-the paramagnetic nanometer-iron nuclides (PNINs) that can be used as both a source for targeted radiotherapy, and a carrier for targeted chemotherapy; to design an in-vitro system of rotating magnetic field as the guiding magnetic field to concentrate PNINs on the target area; to study theoretically and simulate numerically the transport properties and the targeting aggregation characteristics of the PNINs under the guiding magnetic field; to explore the physical target positioning system for targeted therapies of solid tumors with PNINs drugs, which could provide theoretical basis and technical parameters for clinical tumor therapy using PNINs.
Methods:(1) The iron nanoparticles are prepared by chemical carbonyl method, and the paramagnetic nanometer-iron nuclides (PNINs) are produced by irradiating the prepared iron nanoparticles with the pulsed-neutron reactor. (2)The intensities and gradient distributions are compared among the circular current magnetic field, the Helmholtz coil magnetic field, the cylindrical permanent magnetic field, the circular current magnetic field and the rotating magnetic field after adding magnetic materials. Theoretical models for the physical target positioning system of the PNINs in the static magnetic field (target) and in the rotating magnetic field (in vitro) are established and simulated numerically by using ANSYS software; (3) Based on the force distribution on PNINs in the body, a theoretical model for PNINs in the target positioning system is established. Numerical simulation are carried out with MATHCAD procedure for the trajectory of PNINs carrying magnetic drugs in the rotating magnetic field; (4) The transport properties, accumulation characteristics and dynamic behavior of PNINs and drug-loaded PNIPs in the microvasculature under the guiding magnetic field are described, modelled and calculated.
Results:(1) The radioactive nanometer-iron nuclides with average diameter less than 100nm are produced. The nanoparticles exhibite strong paramagnetism, radioactivity intensity and good magnetic delivery function and can be effectively positioned to the target area. (2) The magnetic field of the cylindrical permanent-magnet has the largest magnetic intensity and gradient among the three guiding magnetic fields. Addition of magnetic material into the cylindrical permanent-magnet can raise the magnetic field gradient and the aggregation of the PNINs within the target area, which is essential to targeted therapies. (3) The physical targeting system guided by the rotating magnetic field (in vitro) for the positioning of PNINs can avoid the injuries resulted from the establishment of the static magnetic field (target area). (4) The effects of the size of the magnetic drug particle, the PNINs content, the tumor depth, the blood flow rate, the vessel diameter and other factors on the drug collection rate are obtained.
Conclusions:PNINs and drug-loaded particles in target positioning system, including the in-vivo constant magnetic field and the in-vitro rotating magnetic field, can gather efficiently in the target area with excellent targeting ability. The effect of targeting aggregation can be evaluated quantitatively by calculating the collection rate of PNINs drugs and the coefficient of the capture cross section.
方法：(1)采用化学羰基法制备纳米铁微粒,然后通过脉冲中子反应堆辐照纳米铁制备顺磁纳米铁核素(PNINs);(2)在比较圆形电流磁场、亥姆霍兹线圈磁场、圆柱形永磁场、圆电流磁场和旋转磁场中添加导磁材料后的磁场强度和磁场梯度的分布特点后,对顺磁纳米铁核素(PNINs)在稳恒磁场(靶区)和旋转磁场(体外)引导下的物理靶向定位系统进行理论建模并采用ANSYS软件进行数值计算；(3)根据PNINs在体内的受力情况,建立其在靶向定位系统中的理论模型,利用MATHCAD程序对PNINs磁性药物颗粒在旋转磁场作用下的运行轨迹进行数值模拟；(4)对微血管中单个的顺磁纳米铁核素(PNINs)粒子和包裹有药物的顺磁纳米铁核素(PNINs)微粒在引导磁场作用下的输运特性、富集特征及动力学运动行为进行描述、建模和数值计算。
结果：(1)制得平均粒径<100nm的放射性核素-纳米铁,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；(2)在三种引导磁场中,圆柱形永磁体的磁场分布具有相对较大的磁场强度和梯度,添加导磁材料后,能提高靶区的磁场梯度,促使PNINs局效地聚集靶区,这对靶向治疗至关重要；(3)体外旋转磁场物理靶向定位PNINs,可避免有创伤性的体内靶区稳恒磁场靶向定位；(4)获得了磁性药物的粒径大小、PNINs含量、肿瘤深度、血流速度和血管直径等因素对药物收集率的影响关系。
结论：PNINs及其载药微粒在物理靶向定位系统包括体内恒磁场和体外旋转磁场作用下,能够在靶区高效聚集,具有优异的靶向性；其靶向聚集效果可以通过计算PNINs药物的收集率和俘获截面系数进行定量评价。
Objectives:To develop a new type of material-the paramagnetic nanometer-iron nuclides (PNINs) that can be used as both a source for targeted radiotherapy, and a carrier for targeted chemotherapy; to design an in-vitro system of rotating magnetic field as the guiding magnetic field to concentrate PNINs on the target area; to study theoretically and simulate numerically the transport properties and the targeting aggregation characteristics of the PNINs under the guiding magnetic field; to explore the physical target positioning system for targeted therapies of solid tumors with PNINs drugs, which could provide theoretical basis and technical parameters for clinical tumor therapy using PNINs.
Methods:(1) The iron nanoparticles are prepared by chemical carbonyl method, and the paramagnetic nanometer-iron nuclides (PNINs) are produced by irradiating the prepared iron nanoparticles with the pulsed-neutron reactor. (2)The intensities and gradient distributions are compared among the circular current magnetic field, the Helmholtz coil magnetic field, the cylindrical permanent magnetic field, the circular current magnetic field and the rotating magnetic field after adding magnetic materials. Theoretical models for the physical target positioning system of the PNINs in the static magnetic field (target) and in the rotating magnetic field (in vitro) are established and simulated numerically by using ANSYS software; (3) Based on the force distribution on PNINs in the body, a theoretical model for PNINs in the target positioning system is established. Numerical simulation are carried out with MATHCAD procedure for the trajectory of PNINs carrying magnetic drugs in the rotating magnetic field; (4) The transport properties, accumulation characteristics and dynamic behavior of PNINs and drug-loaded PNIPs in the microvasculature under the guiding magnetic field are described, modelled and calculated.
Results:(1) The radioactive nanometer-iron nuclides with average diameter less than 100nm are produced. The nanoparticles exhibite strong paramagnetism, radioactivity intensity and good magnetic delivery function and can be effectively positioned to the target area. (2) The magnetic field of the cylindrical permanent-magnet has the largest magnetic intensity and gradient among the three guiding magnetic fields. Addition of magnetic material into the cylindrical permanent-magnet can raise the magnetic field gradient and the aggregation of the PNINs within the target area, which is essential to targeted therapies. (3) The physical targeting system guided by the rotating magnetic field (in vitro) for the positioning of PNINs can avoid the injuries resulted from the establishment of the static magnetic field (target area). (4) The effects of the size of the magnetic drug particle, the PNINs content, the tumor depth, the blood flow rate, the vessel diameter and other factors on the drug collection rate are obtained.
Conclusions:PNINs and drug-loaded particles in target positioning system, including the in-vivo constant magnetic field and the in-vitro rotating magnetic field, can gather efficiently in the target area with excellent targeting ability. The effect of targeting aggregation can be evaluated quantitatively by calculating the collection rate of PNINs drugs and the coefficient of the capture cross section.
引文
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