基于纳米组装结构高性能磁共振造影剂的研究及其肝癌诊断应用

The pursuit of high-performance magnetic resonance imaging (MRI) contrast agents has long been advocated due to the effectiveness on enhanced diagnostic accuracy. Magnetic nanoparticle aggregations would show enhanced T2 (dark) contrast efficiency, however, the underlying mechanism is still not clear, which largely hampered the sophisticated design of novel MRI contrast agents based on self-assembly of magnetic nanoparticles. This project propose to investigate the induced magnetic stray field by magnetic coupling effect, which will be performed by model simulation and LLG calculation. According to the theoretical results, this project will utilize several types of iron oxide nanoparticles with different size and morphology as building-blocks for controllable self-assembly to nanostructures, which will be evaluated on their T2 contrast efficacy in mouse liver and in orthotopic liver tumor models. This project intends to clarify the relationships between magnetic coupling and T2 contrast efficiency in self-assembled magnetic nanostructures. Meanwhile, this project will provide valuable design considerations for a series of highly efficient MRI contrast agents, which may furnish the basic understanding and experimental practices for clinical translation of MRI contrast agents based on self-assembled magnetic nanostructures.

发展新颖高效的磁共振成像造影剂对提高病灶诊断的准确性和精确性方面具有重要意义。磁性纳米颗粒聚集体具有增强的T2暗场造影性能，然而其内在机制并不明确，极大地限制了基于磁性纳米组装结构造影剂的优化设计。本项目拟对磁性纳米颗粒的磁耦合相互作用构建模型，计算其所产生的磁场杂散场梯度，结合理论计算结果，采用不同形貌、尺寸的氧化铁纳米颗粒进行可控组装，并在活体水平和小鼠原位肝癌模型中验证其T2暗场造影性能。本项目的实施旨在探明纳米颗粒磁耦合相互作用及其T2弛豫增强效应的构效关系，同时获得一批新颖高效的氧化铁纳米组装体T2造影剂应用于肝癌诊断研究，为推动磁共振造影剂的临床转化奠定理论基础和实验依据。

发展新颖高效的磁共振成像造影剂对提高病灶诊断的准确性和精确性方面具有重要意义。磁性纳米颗粒聚集体具有增强的T2暗场造影性能，然而其内在机制并不明确，极大地限制了基于磁性纳米组装结构造影剂的优化设计。本项目通过对磁性纳米颗粒的磁耦合相互作用构建模型，计算其所产生的磁场杂散场梯度，结合理论计算结果，采用不同形貌、尺寸的氧化铁纳米颗粒进行可控组装，并在活体水平和小鼠原位肝癌模型中验证了其T2暗场造影性能。本项目研究成果表明，通过自组装得到组分为两种不同尺寸的氧化铁纳米颗粒聚集体具有相比于同等条件下其他聚集体较高的T2驰豫效能；组分为两种不同形貌的氧化铁纳米颗粒聚集体具有相比于同等条件下其他聚集体较高的T2驰豫效能。本项目的实施探明了纳米颗粒磁耦合相互作用及其T2弛豫增强效应的构效关系，同时获得一批新颖高效的氧化铁纳米组装体T2造影剂应用于肝癌诊断研究，为推动磁共振造影剂的临床转化奠定理论基础和实验依据。