基于磁场-磁性纳米颗粒非热效应的EGFR过表达肺癌靶向干预机制研究

The intervention of cell multiplication by non-thermal effect of magnetic nanoparticles in magnetic field, an international research hotspot, has preoccupied a growing number of scientists in recent years. However, the mechanism of targeted intervention for EGFR overexpression lung tumor based non-thermal effect of magnetic nanoparticles in magnetic field is not being fully determined. The mechanism is closely related to the shape of the nanoparticles, targeting ability and the formation of the magnetic field. In the present study, the magnetic nanoparticles with the high magnetic responsiveness and targeting ability will be studied and produced by simulation, topological optimization, and surface modification. The relationship between shapes and electromagnetic properties will be determined. The design method of targeted magnetic nanoparticles will also be established. The comparison experiment based on the magnetic intervention platform will be carried out. The effective formation and the range of parameters will be studied based on the surface established by response surface methodology between the proliferative rate of lung tumor cells and magnetic field parameters. Based on the effective formation, the change-rule of the electromagnetic property and biochemical characteristics will be studied by electromagnetic testing and biochemical analysis. The mechanism of targeted intervention for EGFR overexpression lung tumor based non-thermal effect of magnetic nanoparticles in magnetic field will be revealed. This project will take the efforts to complete theoretical system of the bio-effect of the magnetic field and also make a contribution to establish the theoretical foundation of clinical applications.

利用磁场-磁性纳米颗粒非热效应对癌细胞增殖进行干预是近年来国内外的研究热点，然而磁性纳米颗粒对癌细胞增殖的非热效应干预机制有待进一步明确，该机制与磁性纳米颗粒的形貌结构、靶向性及磁场作用形式密切相关。本项目拟开展磁场-磁性纳米颗粒对EGFR过表达肺癌细胞非热效应干预机制的研究，通过电磁场有限元仿真计算、形貌拓扑优化及表面修饰，研制具有高磁响应性和靶向性的磁性纳米颗粒，建立具有靶向性的磁性纳米颗粒设计方法；构建癌细胞增殖磁场干预实验平台，开展细胞对比实验，通过响应曲面法建立肺癌细胞增殖率与磁场参数间的关系曲面，明确磁场的有效作用形式及参数范围；基于磁场有效作用形式，利用电磁、生化检测手段，探索磁场-磁性纳米颗粒协同干预下EGFR过表达肺癌细胞电磁、生化特性变化规律；阐明磁场-磁性纳米颗粒对EGFR过表达肺癌细胞的非热效应干预机制，进一步完善磁场生物学效应的理论体系，为临床应用奠定理论基础。

近年来，我国肺癌的发病率不断攀升，肺癌已经成为威胁人民健康的头号癌症。在传统治疗手段效果均不理想的现实情况下，亟需寻找新的治疗手段，为众多患者带去新的希望。研究表明，外界电磁场会对细胞的电活动造成影响。研究已经证实了磁场对细胞增殖的干预效应，然而不同参数的磁场对细胞增殖具有较大差异。磁性纳米颗粒作为一种新型纳米材料，吸引着众多研究者的目光。利用磁场-磁性纳米颗粒非热效应对癌细胞增殖进行干预成为了近年来的研究热点。然而，面向癌细胞增殖抑制的磁性纳米颗粒及其制备仍需进一步探索，与颗粒协同的磁场有效作用形式仍需深入研究。.本研究依照研究计划，完成了预定的研究工作。首先设计并制备了相关磁性纳米颗粒；为了与所设计的磁性纳米颗粒进行协同，基于电磁场有限元方法，设计并实现了多种磁场线圈方案，针对所需磁场，设计并实现了相关磁场激励源，具有电流、频率可调能力；在此基础上，利用数值分析法，研究了磁性纳米颗粒在磁场协同下的非热效应。结合磁场线圈和磁场激励源，利用所制备的磁性纳米颗粒开展了相关细胞实验，磁场-磁性纳米颗粒协同下对肺癌细胞的增殖抑制接近15%。从实验和仿真两个方面探索了磁场-磁性纳米颗粒非热效应对肺癌细胞的增殖干预机制。本项目的研究成果丰富了癌细胞增殖抑制手段，具有重要的理论意义和应用价值。